106 results on '"Luc Malaval"'
Search Results
2. Inner ear ossification and mineralization kinetics in human embryonic development - microtomographic and histomorphological study
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Céline Richard, Guillaume Courbon, Norbert Laroche, Jean Michel Prades, Laurence Vico, and Luc Malaval
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Medicine ,Science - Abstract
Abstract Little is known about middle and inner ear development during the second and third parts of human fetal life. Using ultra-high resolution Microcomputed Tomography coupled with bone histology, we performed the first quantitative middle and inner ear ossification/mineralization evaluation of fetuses between 17 and 39 weeks of gestational age. We show distinct ossification paces between ossicles, with a belated development of the stapes. A complete cochlear bony covering is observed within the time-frame of the onset of hearing, whereas distinct time courses of ossification for semicircular canal envelopes are observed in relation to the start of vestibular functions. The study evidences a spatio-temporal relationship between middle and inner ear structure development and the onset of hearing and balance, critical senses for the fetal adaptation to birth.
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- 2017
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3. The impairment of osteogenesis in bone sialoprotein (BSP) knockout calvaria cell cultures is cell density dependent.
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Guenaelle Bouet, Wafa Bouleftour, Laura Juignet, Marie-Thérèse Linossier, Mireille Thomas, Arnaud Vanden-Bossche, Jane E Aubin, Laurence Vico, David Marchat, and Luc Malaval
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Medicine ,Science - Abstract
Bone sialoprotein (BSP) belongs to the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family, whose members interact with bone cells and bone mineral. BSP is strongly expressed in bone and we previously showed that BSP knockout (BSP-/-) mice have a higher bone mass than wild type (BSP+/+) littermates, with lower bone remodelling. Because baseline bone formation activity is constitutively lower in BSP-/- mice, we studied the impact of the absence of BSP on in vitro osteogenesis in mouse calvaria cell (MCC) cultures. MCC BSP-/- cultures exhibit fewer fibroblast (CFU-F), preosteoblast (CFU-ALP) and osteoblast colonies (bone nodules) than wild type, indicative of a lower number of osteoprogenitors. No mineralized colonies were observed in BSP-/- cultures, along with little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1. Osteopontin (OPN) is the only SIBLING expressed in standard density BSP-/- culture, at higher levels than in wild type in early culture times. At higher plating density, the effects of the absence of BSP were partly rescued, with resumed expression of osteoblast markers and cognate SIBLING proteins, and mineralization of the mutant cultures. OPN expression and amount are further increased in high density BSP-/- cultures, while PHEX and CatB expression are differentiatlly regulated in a manner that may favor mineralization. Altogether, we found that BSP regulates mouse calvaria osteoblast cell clonogenicity, differentiation and activity in vitro in a cell density dependent manner, consistent with the effective skeletogenesis but the low levels of bone formation observed in vivo. The BSP knockout bone microenvironment may alter the proliferation/cell fate of early osteoprogenitors.
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- 2015
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4. Skeletal development of mice lacking bone sialoprotein (BSP)--impairment of long bone growth and progressive establishment of high trabecular bone mass.
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Wafa Bouleftour, Maya Boudiffa, Ndeye Marième Wade-Gueye, Guénaëlle Bouët, Marco Cardelli, Norbert Laroche, Arnaud Vanden-Bossche, Mireille Thomas, Edith Bonnelye, Jane E Aubin, Laurence Vico, Marie Hélène Lafage-Proust, and Luc Malaval
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Medicine ,Science - Abstract
Adult Ibsp-knockout mice (BSP-/-) display shorter stature, lower bone turnover and higher trabecular bone mass than wild type, the latter resulting from impaired bone resorption. Unexpectedly, BSP knockout also affects reproductive behavior, as female mice do not construct a proper "nest" for their offsprings. Multiple crossing experiments nonetheless indicated that the shorter stature and lower weight of BSP-/- mice, since birth and throughout life, as well as their shorter femur and tibia bones are independent of the genotype of the mothers, and thus reflect genetic inheritance. In BSP-/- newborns, µCT analysis revealed a delay in membranous primary ossification, with wider cranial sutures, as well as thinner femoral cortical bone and lower tissue mineral density, reflected in lower expression of bone formation markers. However, trabecular bone volume and osteoclast parameters of long bones do not differ between genotypes. Three weeks after birth, osteoclast number and surface drop in the mutants, concomitant with trabecular bone accumulation. The growth plates present a thinner hypertrophic zone in newborns with lower whole bone expression of IGF-1 and higher IHH in 6 days old BSP-/- mice. At 3 weeks the proliferating zone is thinner and the hypertrophic zone thicker in BSP-/- than in BSP+/+ mice of either sex, maybe reflecting a combination of lower chondrocyte proliferation and impaired cartilage resorption. Six days old BSP-/- mice display lower osteoblast marker expression but higher MEPE and higher osteopontin(Opn)/Runx2 ratio. Serum Opn is higher in mutants at day 6 and in adults. Thus, lack of BSP alters long bone growth and membranous/cortical primary bone formation and mineralization. Endochondral development is however normal in mutant mice and the accumulation of trabecular bone observed in adults develops progressively in the weeks following birth. Compensatory high Opn may allow normal endochondral development in BSP-/- mice, while impairing primary mineralization.
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- 2014
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5. Sexe, genre et stature
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Ghislain Nicaise and Luc Malaval
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General Medicine ,General Biochemistry, Genetics and Molecular Biology - Abstract
Dans l’espèce humaine, l’origine du dimorphisme sexuel de stature est l’objet de controverses. Sa composante héréditaire pourrait dépendre principalement du déterminisme endocrinien de l’arrêt de croissance à la puberté. C’est l’explication la plus simple, une explication qui apparaît également valable pour la plupart des mammifères. L’ossification des cartilages de conjugaison, qui signe l’arrêt de croissance des os longs, se produit d’abord chez les femelles (les jeunes femmes) puis chez les mâles. Dans les deux sexes, elle reste contrôlée par l’augmentation du taux d’œstrogènes. L’avantage reproductif conféré par les œstrogènes permettrait d’expliquer la relativement petite taille des femmes, en dépit des difficultés obstétriques associées à cette petite taille.
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- 2022
6. [Sex, gender and stature: From biology to culture - and back]
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Ghislain, Nicaise and Luc, Malaval
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Male ,Mammals ,Sex Characteristics ,Fertility ,Pregnancy ,Animals ,Body Size ,Humans ,Estrogens ,Female ,Biology ,Body Height - Abstract
The origin of sexual dimorphism of stature (SSD) in the human species is a subject of debate, likely to have a sociocultural impact. Stature is optimally expressed in good environmental conditions, notably good food, with a strong hereditary determinism. The common academic interpretation, already proposed by Darwin, is that SSD results from sexual selection of stronger males, in most species of mammals, including humans. An alternative hypothesis proposes that it might result from alimentary gender coercion in humans. There is practically no SSD until female growth stops, by ossification of cartilage in the growth plates of long bones, largely under the action of estrogens. The mechanism is the same in males, with a delay due to a lesser and/or later concentration of estrogens. This explanation for SSD has the advantage of being valid for most mammalian species, including those like Pan paniscus where females are dominant. The fitness resulting from high estrogen levels would explain the relatively small stature of women, in spite of obstetric difficulties inversely correlated with height. If patriarchy is involved, it would be by the injunction of fertility rather than by alimentary coercion.Sexe, genre et stature - De la biologie à la culture - et retour.Dans l’espèce humaine, l’origine du dimorphisme sexuel de stature est l’objet de controverses. Sa composante héréditaire pourrait dépendre principalement du déterminisme endocrinien de l’arrêt de croissance à la puberté. C’est l’explication la plus simple, une explication qui apparaît également valable pour la plupart des mammifères. L’ossification des cartilages de conjugaison, qui signe l’arrêt de croissance des os longs, se produit d’abord chez les femelles (les jeunes femmes) puis chez les mâles. Dans les deux sexes, elle reste contrôlée par l’augmentation du taux d’œstrogènes. L’avantage reproductif conféré par les œstrogènes permettrait d’expliquer la relativement petite taille des femmes, en dépit des difficultés obstétriques associées à cette petite taille.
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- 2022
7. Knockout of osteopontin or bone sialoprotein induces opposite response to mechanical stimulation
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Laurence Vico, Mathieu Maalouf, Mireille Thomas, Luc Malaval, Alain Guignandon, Wafa Bouleftour-Esquis, Arnaud Vanden-Boscche, Norbert Laroche, and Hawa Cinar
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Bone sialoprotein ,biology ,RC925-935 ,Chemistry ,Endocrinology, Diabetes and Metabolism ,biology.protein ,Orthopedics and Sports Medicine ,Stimulation ,Osteopontin ,Diseases of the musculoskeletal system ,Cell biology - Published
- 2021
8. Bone Shaft Revascularization After Marrow Ablation Is Dramatically Accelerated in BSP-/- Mice, Along With Faster Hematopoietic Recolonization
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Marie Thérèse Linossier, Arnaud Vanden-Bossche, Odile Sabido, Laurence Vico, Mireille Thomas, Bernard Roche, Wafa Bouleftour, Luc Malaval, Jane E. Aubin, Marie-Hélène Lafage-Proust, and Renata neves Granito
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0301 basic medicine ,Bone sialoprotein ,biology ,Medullary cavity ,Physiology ,Chemistry ,Clinical Biochemistry ,Cell Biology ,Bone tissue ,Andrology ,03 medical and health sciences ,Bone Marrow Ablation ,fluids and secretions ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,stomatognathic system ,030220 oncology & carcinogenesis ,Immunology ,medicine ,biology.protein ,Bone organ ,Bone marrow ,Osteopontin ,Integrin binding - Abstract
The bone organ integrates the activity of bone tissue, bone marrow, and blood vessels and the factors ensuring this coordination remain ill defined. Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis. In rodents, bone marrow ablation induces a rapid formation of medullary bone which peaks by ∼8 days (d8) and is blunted in BSP-/- mice. We investigated the coordinate hematopoietic and vascular recolonization of the bone shaft after marrow ablation of 2 month old BSP+/+ and BSP-/- mice. At d3, the ablated area in BSP-/- femurs showed higher vessel density (×4) and vascular volume (×7) than BSP+/+. Vessel numbers in the shaft of ablated BSP+/+ mice reached BSP-/- values only by d8, but with a vascular volume which was twice the value in BSP-/-, reflecting smaller vessel size in ablated mutants. At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization. However, the proportion of LSK and HSC within the Lin- was lower in BSP-/- and more differentiated stages were more abundant, as also observed in unablated bone, suggesting that hematopoietic differentiation is favored in the absence of BSP. Interestingly, unablated BSP-/- femur marrow also contains more blood vessels than BSP+/+, and in both intact and ablated shafts expression of VEGF and OPN are higher, and DMP1 lower in the mutants. In conclusion, bone marrow ablation in BSP-/- mice is followed by a faster vascular and hematopoietic recolonization, along with lower medullary bone formation. Thus, lack of BSP affects the interplay between hematopoiesis, angiogenesis, and osteogenesis, maybe in part through higher expression of VEGF and the angiogenic SIBLING, OPN. J. Cell. Physiol. 232: 2528-2537, 2017. © 2016 Wiley Periodicals, Inc.
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- 2017
9. Macrotopographic closure promotes tissue growth and osteogenesis in vitro
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Baptiste Charbonnier, Laurence Vico, Nathalie Douard, Virginie Dumas, Luc Malaval, Coralie Laurent, Laura Juignet, David Marchat, Wafa Bouleftour, Mireille Thomas, Biologie intégrative du tissu osseux, Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Fédératif de Recherche en Sciences et Ingénierie de la Santé (IFRESIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-IFR143, Ingénierie des Biomatériaux et des Particules Inhalées (BIOPI-ENSMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-CIS, INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre Ingénierie et Santé (CIS-ENSMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Laboratoire de Tribologie et Dynamique des Systèmes (LTDS), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Ecole Nationale d'Ingénieurs de Saint Etienne-Centre National de la Recherche Scientifique (CNRS), Laboratoire Georges Friedel (LGF-ENSMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Ecole Nationale d'Ingénieurs de Saint Etienne (ENISE)-Centre National de la Recherche Scientifique (CNRS), and juignet, laura
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0301 basic medicine ,Materials science ,Surface Properties ,[SDV]Life Sciences [q-bio] ,Cellular differentiation ,Biomedical Engineering ,Nanotechnology ,Calvaria ,02 engineering and technology ,Matrix (biology) ,MESH: Bioceramics ,Macrotopography ,Osteoblast differentiation ,Substrate closure ,Biochemistry ,Biomaterials ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Osteogenesis ,Materials Testing ,Bone cell ,Cell Adhesion ,medicine ,Animals ,Molecular Biology ,Cells, Cultured ,Cell Proliferation ,Osteoblasts ,biology ,Cell Differentiation ,Osteoblast ,General Medicine ,021001 nanoscience & nanotechnology ,Cell biology ,[SDV] Life Sciences [q-bio] ,Durapatite ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Osteocyte ,Bone Substitutes ,Osteocalcin ,biology.protein ,Sclerostin ,0210 nano-technology ,Biotechnology - Abstract
While the impact of substrate topographies at nano- and microscale on bone cell behavior has been particularly well documented, very few studies have analyzed the role of substrate closure at a tissular level. Moreover, these have focused on matrix deposition rather than on osteoblastic differentiation. In the present work, mouse calvaria cells were grown for 15 days on hydroxyapatite (HA) ceramics textured with three different macrogrooves shapes ( ** 100 µm): 1 sine and 2 triangle waveforms. We found that macrotopography favors cell attachment, and that bone-like tissue growth and organization are promoted by a tight “closure angle” of the substrate geometry. Interestingly, while Flat HA controls showed little marker expression at the end of the culture, cells grown on macrogrooves, and in particular the most closed (triangle waveform with a 517 µm spatial period) showed a fast time-course of osteoblast differentiation, reaching high levels of gene and protein expression of osteocalcin and sclerostin, a marker of osteocytes. Statement of Significance Many in vitro studies have been conducted on topography at nano and microscale, fewer have focused on the influence of macrotopography on osteoblasts. Ceramics with a controlled architecture were obtained throught a 3D printing process and used to assess osteoblast behavior. Biocompatible, they allowed the long-terme survival of osteoblast cells and the laying of an important bone matrix. V-shaped grooves were found to accelerates osteoblast differentiation and promote bone-like tissue deposition and maturation (osteocyte formation), proportionately to angle closure. Such macrostructures are attractive for the design of innovative implants for bone tissue engineering and in vitro models of osteogenesis.
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- 2017
10. Deletion of OPN in BSP knockout mice does not correct bone hypomineralization but results in high bone turnover
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Evelyne Gineyts, Norbert Laroche, Arnaud Vanden-Bossche, Luc Malaval, Olivier Peyruchaud, D. Aubert, L. Verdière, Wafa Bouleftour, C. Thomas, Irma Machuca-Gayet, L. Juignet, Marie-Hélène Lafage-Proust, Hélène Follet, Laurence Vico, Jean-Paul Concordet, Delphine Farlay, Mireille Thomas, M. Teixeira, J.B. Renaud, Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), School of Applied Sciences, University of Glamorgan, Trefforest, Pontypridd, UK CF37, School of Applied Sciences, Tissu Osseux et Contraintes Mecaniques (LBTO), Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie intégrative du tissu osseux, Ostéoporose et Qualité osseuse (Site Laennec), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR62-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de géochimie de la surface (CGS), Institut national des sciences de l'Univers (INSU - CNRS)-Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie Intégrative du Tissu Osseux (LBTO), and Centre National de la Recherche Scientifique (CNRS)-Université Louis Pasteur - Strasbourg I-Institut national des sciences de l'Univers (INSU - CNRS)
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0301 basic medicine ,Bone sialoprotein ,Histology ,Physiology ,Endocrinology, Diabetes and Metabolism ,[SDV]Life Sciences [q-bio] ,Bone Matrix ,Osteoclasts ,030209 endocrinology & metabolism ,Bone and Bones ,Bone remodeling ,03 medical and health sciences ,0302 clinical medicine ,Calcification, Physiologic ,stomatognathic system ,Bone Marrow ,Osteogenesis ,Bone cell ,Animals ,Integrin-Binding Sialoprotein ,Osteopontin ,SIBLING proteins ,ComputingMilieux_MISCELLANEOUS ,Mice, Knockout ,Extracellular Matrix Proteins ,Osteoblasts ,biology ,Chemistry ,[SDV.BA]Life Sciences [q-bio]/Animal biology ,Reproducibility of Results ,Cell Differentiation ,Cell biology ,Resorption ,030104 developmental biology ,Primary bone ,Gene Expression Regulation ,Cancellous Bone ,MEPE ,biology.protein ,Bone Remodeling ,Biomarkers ,Gene Deletion - Abstract
The two SIBLING (Small Integrin Binding Ligand N-linked Glycoproteins), bone sialoprotein (BSP) and osteopontin (OPN) are expressed in osteoblasts and osteoclasts. In mature BSP knockout (KO, -/-) mice, both bone formation and resorption as well as mineralization are impaired. OPN-/- mice display impaired resorption, and OPN is described as an inhibitor of mineralization. However, OPN is overexpressed in BSP-/- mice, complicating the understanding of their phenotype. We have generated and characterized mice with a double KO (DKO) of OPN and BSP, to try and unravel their respective contributions. Despite the absence of OPN, DKO bones are still hypomineralized. The SIBLING, matrix extracellular phosphoglycoprotein with ASARM motif (MEPE) is highly overexpressed in both BSP-/- and DKO and may impair mineralization through liberation of its ASARM (Acidic Serine-Aspartate Rich MEPE associated) peptides. DKO mice also display evidence of active formation of trabecular, secondary bone as well as primary bone in the marrow-ablation repair model. A higher number of osteoclasts form in DKO marrow cultures, with higher resorption activity, and DKO long bones display a localized and conspicuous cortical macroporosity. High bone formation and resorption parameters, and high cortical porosity in DKO mice suggest an active bone modeling/remodeling, in the absence of two key regulators of bone cell performance. This first double KO of SIBLING proteins thus results in a singular, non-trivial phenotype leading to reconsider the interpretation of each single KO, concerning in particular matrix mineralization and the regulation of bone cell activity.
- Published
- 2019
11. Parathyroid Hormone Remodels Bone Transitional Vessels and the Leptin Receptor-Positive Pericyte Network in Mice
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Robin Caire, Carmen-Mariana Aanei, Zhiguo He, Luc Malaval, Bernard Roche, Mireille Thomas, Laurence Vico, Marie-Hélène Lafage-Proust, Lydia Campos, and Tiphanie Picot
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0301 basic medicine ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Parathyroid hormone ,Neovascularization, Physiologic ,030209 endocrinology & metabolism ,Hindlimb ,Bone and Bones ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,Orthopedics and Sports Medicine ,Leptin receptor ,Chemistry ,Leptin ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Gene Expression Regulation ,Parathyroid Hormone ,Receptors, Leptin ,Female ,Bone marrow ,Pericyte ,Endostatin ,Pericytes - Abstract
Intermittent parathyroid hormone (iPTH) is anti-osteoporotic and affects bone vessels. Transitional capillaries close to the bone surface, which express both endomucin (Edm) and CD31, bear leptin receptor-expressing (LepR) perivascular cells that may differentiate into osteoblasts. Increased numbers of type H endothelial cells (THEC; ie, Edmhi /CD31hi cells assessed by flow cytometry, FACS) are associated with higher bone formation in young mice. We hypothesized that iPTH administration impacts transitional vessels by expanding THECs. Four-month-old C57/Bl6J female mice were injected with PTH 1-84 (100 μg/kg/d) or saline (CT) for 7 or 14 days. We quantified LepR+ , CD31+ , Edm+ cells and THECs by FACS in hindlimb bone marrow, and Edm/LepR double immunolabelings on tibia cryosections. Additionally, we analyzed bone mRNA expression of 87 angiogenesis-related genes in mice treated with either intermittent or continuous PTH (iPTH/cPTH) or saline (CT) for 7, 14, and 28 days. iPTH dramatically decreased the percentage of THECs by 78% and 90% at days 7 and 14, respectively, and of LepR+ cells at day 14 (-46%) versus CT. Immunolabeling quantification showed that the intracortical Edm+ -vessel density increased at day 14 under iPTH. In the bone marrow, perivascular LepR+ cells, connected to each other via a dendrite network, were sparser under iPTH at day 14 (-58%) versus CT. iPTH decreased LepR+ cell coverage of transitional vessels only (-51%), whereas the number of LepR+ cells not attached to vessels increased in the endocortical area only (+ 49%). Transcriptomic analyses showed that iPTH consistently upregulated PEDF, Collagen-18α1, and TIMP-1 mRNA expression compared with CT and cPTH. Finally, iPTH increased immunolabeling of endostatin, a Collagen-18 domain that can be cleaved and become antiangiogenic, in both endocortical (79%) and peritrabecular transitional microvessels at day 14. Our results show that iPTH specifically remodels transitional vessels and suggest that it promotes LepR+ cell mobilization from these vessels close to the bone surface. © 2019 American Society for Bone and Mineral Research.
- Published
- 2018
12. Absence of Bone Sialoprotein (BSP) Alters Profoundly Hematopoiesis and Upregulates Osteopontin
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Wafa Bouleftour, Jane E. Aubin, Mireille Thomas, Renata neves Granito, Laurence Vico, Chloé Lescale, Luc Malaval, Michele Goodhardt, and Odile Sabido
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Bone sialoprotein ,biology ,Physiology ,Clinical Biochemistry ,Hematopoietic stem cell ,Cell Biology ,Bone tissue ,Cell biology ,Haematopoiesis ,medicine.anatomical_structure ,stomatognathic system ,Bone cell ,Immunology ,biology.protein ,medicine ,Osteopontin ,Bone marrow ,B cell - Abstract
Matrix proteins of the SIBLING family interact with bone cells, extracellular matrix and mineral and are thus in a key position to regulate the microenvironment of the bone tissue, including its hematopoietic component. In this respect, osteopontin (OPN) has been implicated in the hematopoietic stem cell (HSC) niche as negative regulator of the HSC function. We investigated the impact on hematopoietic regulation of the absence of the cognate bone sialoprotein (BSP). BSP knockout (−/−) mice display increased bone marrow cellularity, and an altered commitment of hematopoietic precursors to myeloid lineages, leading in particular to an increased frequency of monocyte/macrophage cells. The B cell pool is increased in −/− bone marrow, and its composition is shifted toward more mature lymphocyte stages. BSP-null mice display a decreased HSC fraction among LSK cells and a higher percentage of more committed progenitors as compared to +/+. The fraction of proliferating LSK progenitors is higher in −/− mice, and after PTH treatment the mutant HSC pool is lower than in +/+. Strikingly, circulating levels of OPN as well as its expression in the bone tissue are much higher in the −/−. Thus, a BSP-null bone microenvironment affects the hematopoietic system both quantitatively and qualitatively, in a manner in part opposite to the OPN knockout, suggesting that the effects might in part reflect the higher OPN expression in the absence of BSP. J. Cell. Physiol. 230: 1342–1351, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
- Published
- 2015
13. Blocking the Expression of Both Bone Sialoprotein (BSP) and Osteopontin (OPN) Impairs the Anabolic Action of PTH in Mouse Calvaria Bone
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Jane E. Aubin, Wafa Bouleftour, Laurence Vico, Marie-Hélène Lafage-Proust, Luc Malaval, Mireille Thomas, Guenaelle Bouet, Arnaud Vanden-Bossche, Marie-Thérèse Linossier, and Renata Neves Granito
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musculoskeletal diseases ,Bone sialoprotein ,medicine.medical_specialty ,biology ,Physiology ,Chemistry ,Osteoid ,Clinical Biochemistry ,Parathyroid hormone ,Calvaria ,Osteoblast ,Cell Biology ,musculoskeletal system ,medicine.anatomical_structure ,Endocrinology ,stomatognathic system ,Internal medicine ,medicine ,biology.protein ,MEPE ,Osteocalcin ,Osteopontin - Abstract
Osteopontin (OPN) and bone sialoprotein (BSP) are coexpressed in osteoblasts and osteoclasts, and display overlapping properties. We used daily injection of parathyroid hormone 1–84 (iPTH) over the calvaria of BSP knockout (−/−) mice to investigate further their functional specificity and redundancy. iPTH stimulated bone formation in both +/+ and −/− mice, increasing to the same degree periosteum, osteoid and total bone thickness. Expression of OPN, osterix, osteocalcin (OCN) and DMP1 was also increased by iPTH in both genotypes. In contrast to +/+, calvaria cell cultures from −/− mice revealed few osteoblast colonies, no mineralization and little expression of OCN, MEPE or DMP1. In contrast, OPN levels were 5× higher in −/− versus +/+ cultures. iPTH increased alkaline phosphatase (ALP) activity in cell cultures of both genotypes, with higher OCN and the induction of mineralization in −/− cultures. siRNA blocking of OPN expression did not alter the anabolic action of the hormone in BSP +/+ calvaria, while it blunted iPTH effects in −/− mice, reduced to a modest increase in periosteum thickness. In −/− (not +/+) cell cultures, siOPN blocked the stimulation by iPTH of ALP activity and OCN expression, as well as the induction of mineralization. Thus, full expression of either OPN or BSP is necessary for the anabolic effect of PTH at least in the ectopic calvaria injection model. This suggests that OPN may compensate for the lack of BSP in the response to this hormonal challenge, and provides evidence of functional overlap between these cognate proteins. J. Cell. Physiol. 230: 568–577, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
- Published
- 2014
14. Inner ear ossification and mineralization kinetics in human embryonic development - microtomographic and histomorphological study
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Norbert Laroche, Guillaume Courbon, Luc Malaval, Céline Richard, Laurence Vico, and Jean Michel Prades
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0301 basic medicine ,Science ,Ear, Middle ,Gestational Age ,Biology ,Article ,Fetal Development ,03 medical and health sciences ,Calcification, Physiologic ,Fetus ,0302 clinical medicine ,Hearing ,Osteogenesis ,Pregnancy ,medicine ,otorhinolaryngologic diseases ,Humans ,Human embryogenesis ,Inner ear ,Fetal Death ,Postural Balance ,Stapes ,Vestibular system ,Multidisciplinary ,Semicircular canal ,Ossicles ,Ossification ,X-Ray Microtomography ,Anatomy ,Abortion, Spontaneous ,030104 developmental biology ,medicine.anatomical_structure ,Ear, Inner ,Middle ear ,Medicine ,Female ,sense organs ,medicine.symptom ,Calcification, Physiologic/physiology ,Ear, Inner/anatomy & histology ,Ear, Inner/diagnostic imaging ,Ear, Inner/growth & development ,Ear, Middle/anatomy & histology ,Ear, Middle/diagnostic imaging ,Ear, Middle/growth & development ,Fetal Development/physiology ,Fetus/anatomy & histology ,Fetus/diagnostic imaging ,Hearing/physiology ,Osteogenesis/physiology ,Postural Balance/physiology ,030217 neurology & neurosurgery - Abstract
Little is known about middle and inner ear development during the second and third parts of human fetal life. Using ultra-high resolution Microcomputed Tomography coupled with bone histology, we performed the first quantitative middle and inner ear ossification/mineralization evaluation of fetuses between 17 and 39 weeks of gestational age. We show distinct ossification paces between ossicles, with a belated development of the stapes. A complete cochlear bony covering is observed within the time-frame of the onset of hearing, whereas distinct time courses of ossification for semicircular canal envelopes are observed in relation to the start of vestibular functions. The study evidences a spatio-temporal relationship between middle and inner ear structure development and the onset of hearing and balance, critical senses for the fetal adaptation to birth.
- Published
- 2017
15. Parathyroid Hormone 1-84 Targets Bone Vascular Structure and Perfusion in Mice: Impacts of Its Administration Regimen and of Ovariectomy
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Arnaud Vanden-Bossche, Martin Jannot, Bernard Roche, Marie-Hélène Lafage-Proust, Robin Chaux, Laurence Vico, Myriam Normand, and Luc Malaval
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endocrine system ,medicine.medical_specialty ,Vasomotor ,business.industry ,Endocrinology, Diabetes and Metabolism ,Parathyroid hormone ,Vasodilation ,Propranolol ,Bone remodeling ,Resorption ,Endocrinology ,Internal medicine ,medicine ,Orthopedics and Sports Medicine ,business ,Perfusion ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug ,Hormone - Abstract
Bone vessel functions during bone remodeling are poorly understood. They depend on both vessel network structure and vasomotor regulation. Parathyroid hormone (PTH) is a systemic vasodilator that may modulate microvascularization. Moreover, although intermittent PTH is anti-osteoporotic, continuous PTH administration can be catabolic for bone. Finally, ovariectomy (OVX) reduces bone perfusion and vessel density in mice. We reasoned that the effects of PTH on bone vascularization might depend on its administration regimen and be impacted by ovariectomy. A 100-µg/kg PTH 1-84 daily dose was administered for 15 days to 4-month-old female C57BL/6 mice, either as daily sc injection (iPTH) or continuously (cPTH; ALZET minipump). Blood pressure (BP) and tibia bone perfusion were measured in vivo with a laser Doppler device. Histomorphometry of bone and barium-contrasted vascular network were performed on the same tibia. Compared with untreated controls, both iPTH and cPTH increased bone formation but had opposite effects on resorption. Both iPTH and cPTH were slightly angiogenic. Intermittent PTH increased microvessel size (+48%, p
- Published
- 2014
16. Physico-Chemical Characterization and In Vitro Biological Evaluation of Pure SiHA for Bone Tissue Engineering Application
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David Marchat, Jérôme Chevalier, Aline Ludeckgen, Guenaelle Bouet, Didier Bernache-Assollant, Stéphanie Szenknect, Luc Malaval, Maria Zymelka, and Nicolas Dacheux
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Materials science ,Mechanical Engineering ,0206 medical engineering ,Pellets ,Biomaterial ,02 engineering and technology ,Bioceramic ,021001 nanoscience & nanotechnology ,020601 biomedical engineering ,Chemical engineering ,Mechanics of Materials ,Phase (matter) ,Pellet ,General Materials Science ,Hydroxyapatites ,Solubility ,0210 nano-technology ,Dissolution ,Biomedical engineering - Abstract
Studies about silicon-substituted hydroxyapatites exhibit several shortcomings that leave unanswered questions regarding the properties and subsequent biological outcomes generated by this biomaterial. Firstly, samples characterization is often incomplete, meaning that phase purity on the pellet surface is not assured. In fact, ceramic materials used in literature that are claimed to be pure are actually polluted through second phase as superficial polymerized silicate. In this study, we have successfully synthesized a phase pure silicon hydroxyapatite powder Ca10(PO4)5.5(SiO4)0.5(OH)1.5 (Si0.5HA) compressed this powder into pellets, sintered them, and evaluated the biological response of osteoblast cells (C3H10 line) seeded on the pellet surface. Besides, the solubility in aqueous media of HA and Si0.5HA pellets were determined through static experiments. These tests attempt to provide a comprehensive picture of the cellular response to the SiHA material, in order to determine the mechanism by which Si evokes the improved in vitro biological outcomes described in the literature. Results revealed first an equivalent solubility of Si0.5HA and HA pellets, and second that cells do not react favourably to the pure SiHA surface.
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- 2012
17. Bone Shaft Revascularization After Marrow Ablation Is Dramatically Accelerated in BSP-/- Mice, Along With Faster Hematopoietic Recolonization
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Luc Malaval, Jane E. Aubin, Odile Sabido, Marie-Hélène Lafage-Proust, Arnaud Vanden Bossche, Marie-Thérèse Linossier, Renata Neves Granito, Mireille Thomas, Bernard Roche, Wafa Bouleftour, and Laurence Vico
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Ablation Techniques ,Male ,Vascular Endothelial Growth Factor A ,medicine.medical_specialty ,Time Factors ,Genotype ,medicine.medical_treatment ,Neovascularization, Physiologic ,Revascularization ,Bone Marrow ,Osteogenesis ,medicine ,Animals ,Integrin-Binding Sialoprotein ,Femur ,Cell Proliferation ,Mice, Knockout ,Extracellular Matrix Proteins ,business.industry ,General Medicine ,Ablation ,Hematopoietic Stem Cells ,Surgery ,Hematopoiesis ,Haematopoiesis ,Bone shaft ,Phenotype ,Osteopontin ,business ,Biomarkers ,Signal Transduction - Abstract
The bone organ integrates the activity of bone tissue, bone marrow, and blood vessels and the factors ensuring this coordination remain ill defined. Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis. In rodents, bone marrow ablation induces a rapid formation of medullary bone which peaks by ∼8 days (d8) and is blunted in BSP-/- mice. We investigated the coordinate hematopoietic and vascular recolonization of the bone shaft after marrow ablation of 2 month old BSP+/+ and BSP-/- mice. At d3, the ablated area in BSP-/- femurs showed higher vessel density (×4) and vascular volume (×7) than BSP+/+. Vessel numbers in the shaft of ablated BSP+/+ mice reached BSP-/- values only by d8, but with a vascular volume which was twice the value in BSP-/-, reflecting smaller vessel size in ablated mutants. At d6, a much higher number of Lin
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- 2016
18. Structure and quantification of microvascularisation within mouse long bones: What and how should we measure?
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Marie-Hélène Lafage-Proust, Laurence Vico, Arnaud Vanden-Bossche, Bernard Roche, Françoise Peyrin, Valentin David, Luc Malaval, Biologie intégrative du tissu osseux, Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Health Science Center, The University of Tennessee [Knoxville], European Synchrotron Radiation Facility (ESRF), Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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Male ,CD31 ,Pathology ,medicine.medical_specialty ,Histology ,Physiology ,Ovariectomy ,Endocrinology, Diabetes and Metabolism ,Long bone ,030209 endocrinology & metabolism ,Hindlimb ,Microcirculation ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Bone cell ,Animals ,Humans ,Medicine ,Tibia ,030304 developmental biology ,0303 health sciences ,business.industry ,X-Ray Microtomography ,Anatomy ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Blood Vessels ,Female ,Bone marrow ,Barium Sulfate ,business ,[SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing - Abstract
International audience; Bone marrow vascularisation is involved in both remodeling and hematopoïesis. Challenged mouse models often require imaging and quantitative assessment of blood vessels and bone cell activities for a better understanding of the role of the vascular system. In this study we compared images of mouse hind limb long bone vascularisation after infusion of either barium sulfate or lead chromate-loaded silicon. The images were then analyzed through histology as well as low-resolution and synchrotron-radiation microtomography. We show that barium sulfate infusion provides the best vessel images and furthermore, that it is compatible with staining procedures used in bone histomorphometry and CD31 immunohistochemistry. Bone marrow vascularisation displays large structural and spatial distribution heterogeneity, including large lobular clusters of sinusoids and an unexpectedly substantial amount of capillaries in the adipocytes-rich distal third of the tibia. For an unbiased assessment of bone vascular development/changes, these features must be taken into account. We describe the conditions under which the quantification of microvascularisation on histological sections of barium-infused long bones is reproducible, as applied to seven-month-old male C57/Bl6J and mixed CD1/129Sv/J mice, and we propose a nomenclature for the histological parameters measured. Finally, we validate our technique by studying the effect of ovariectomy on mouse tibial vascular density.
- Published
- 2012
19. Intermittent PTH(1-84) is osteoanabolic but not osteoangiogenic and relocates bone marrow blood vessels closer to bone-forming sites
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Max Langer, Rhonda D. Prisby, Luc Malaval, Alain Guignandon, Françoise Peyrin, Marie-Hélène Lafage-Proust, Marie-Thérèse Linossier, Zoltz-Andrei Peter, Arnaud Vanden-Bossche, Norbert Laroche, Laurence Vico, Mireille Thomas, and Fabrice Mac-Way
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medicine.medical_specialty ,Anabolism ,business.industry ,Angiogenesis ,Endocrinology, Diabetes and Metabolism ,Parathyroid hormone ,Bone remodeling ,Vascular endothelial growth factor ,chemistry.chemical_compound ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Internal medicine ,Neuropilin 1 ,medicine ,Neuropilin ,Orthopedics and Sports Medicine ,Bone marrow ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
Intermittent parathyroid hormone (PTH) is anabolic for bone. Our aims were to determine (1) whether PTH stimulates bone angiogenesis and (2) whether vascular endothelial growth factor (VEGF A) mediates PTH-induced bone accrual. Male Wistar rats were given PTH(1–84) daily, and trabecular bone mass increased 150% and 92% after 30 and 15 days, respectively. The vascular system was contrasted to image and quantify bone vessels with synchrotron radiation microtomography and histology. Surprisingly, bone vessel number was reduced by approximately 25% and approximately 40% on days 30 and 15, respectively. PTH redistributed the smaller vessels closer to bone-formation sites. VEGF A mRNA expression in bone was increased 2 and 6 hours after a single dose of PTH and returned to baseline by 24 hours. Moreover, anti-VEGF antibody administration (1) blunted the PTH-induced increase in bone mass and remodeling parameters, (2) prevented the relocation of bone vessels closer to bone-forming sites, and (3) inhibited the PTH-induced increase in mRNA of neuropilin 1 and 2, two VEGF coreceptors associated with vascular development and function. In conclusion, PTH(1–84) is osteoanabolic through VEGF-related mechanism(s). Further, PTH spatially relocates blood vessels closer to sites of new bone formation, which may provide a microenvironment favorable for growth. © 2011 American Society for Bone and Mineral Research
- Published
- 2011
20. Thyroid hormone receptor β mediates thyroid hormone effects on bone remodeling and bone mass
- Author
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Bénédicte Rabier, Johan Photsavang, Adrienne Anginot, Laurence Vico, Olivier Chassande, Luc Malaval, Romain Dacquin, Laurent-Emmanuel Monfoulet, and Pierre Jurdic
- Subjects
Aging ,Thyroid Hormones ,medicine.medical_specialty ,Bone density ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Bone and Bones ,Bone resorption ,Bone remodeling ,Thyroid hormone receptor beta ,Mice ,Bone Density ,Osteogenesis ,Osteoclast ,Internal medicine ,medicine ,Animals ,Orthopedics and Sports Medicine ,Bone Resorption ,Mice, Knockout ,Thyroid hormone receptor ,Chemistry ,Thyroid Hormone Receptors beta ,Organ Size ,medicine.disease ,Hyperthyroxinemia ,Endocrinology ,medicine.anatomical_structure ,Thyroid hormone receptor alpha ,Triiodothyronine ,Bone Remodeling ,Thyroid Hormone Receptors alpha - Abstract
Excess thyroid hormone (TH) in adults causes osteoporosis and increases fracture risk. However, the mechanisms by which TH affects bone turnover are not elucidated. In particular, the roles of thyroid hormone receptor (TR) isotypes in the mediation of TH effects on osteoblast-mediated bone formation and osteoclast-mediated bone resorption are not established. In this study we have induced experimental hypothyroidism or hyperthyroidism in adult wild-type, TRα- or TRβ-deficient mice and analyzed the effects of TH status on the structure and remodeling parameters of trabecular bone. In wild-type mice, excess TH decreased bone volume and mineralization. High TH concentrations were associated with a high bone-resorption activity, assessed by increased osteoclast surfaces and elevated concentrations of serum bone-resorption markers. Serum markers of bone formation also were higher in TH-treated mice. TRα deficiency did not prevent TH action on bone volume, bone mineralization, bone formation, or bone resorption. In contrast, TRβ deficiency blocked all the early effects of excess TH observed in wild-type mice. However, prolonged exposure to low or high TH concentrations of TRβ-deficient mice induced mild modifications of bone structure and remodeling parameters. Together our data suggest that TRβ receptors mediate the acute effects produced by transient changes of TH concentrations on bone remodeling, whereas TRα receptors mediate long-term effects of chronic alterations of TH metabolism. These data shed new light on the respective roles of TRs in the control of bone metabolism by TH.
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- 2011
21. Bone sialoprotein, but not osteopontin, deficiency impairs the mineralization of regenerating bone during cortical defect healing
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Alain P. Gadeau, Susan R. Rittling, Laurent Monfoulet, Olivier Chassande, Luc Malaval, Jean-Christophe Fricain, Jane E. Aubin, Biologie intégrative du tissu osseux, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM), Department of Molecular and Medical Genetics, University of Toronto, Bioingénierie tissulaire (BIOTIS), and Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Bone sialoprotein ,Pathology ,medicine.medical_specialty ,Bone Regeneration ,Histology ,Physiology ,[SDV]Life Sciences [q-bio] ,Sialoglycoproteins ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Bone healing ,Bone remodeling ,Mice ,03 medical and health sciences ,Calcification, Physiologic ,0302 clinical medicine ,stomatognathic system ,Osteogenesis ,[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,Bone cell ,medicine ,Animals ,Integrin-Binding Sialoprotein ,Femur ,Bone regeneration ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Wound Healing ,0303 health sciences ,biology ,Chemistry ,X-Ray Microtomography ,Anatomy ,medicine.anatomical_structure ,Primary bone ,Gene Expression Regulation ,Intramembranous ossification ,biology.protein ,Osteopontin ,Cortical bone ,Diaphyses - Abstract
Bone healing is a complex multi-step process, which depends on the position and size of the lesion, and on the mechanical stability of the wounded area. To address more specifically the mechanisms involved in cortical bone healing, we created drill-hole defects in the cortex of mouse femur, a lesion that triggers intramembranous repair, and compared the roles of bone sialoprotein (BSP) and osteopontin (OPN), two proteins of the extracellular matrix, in the repair process. Bone regeneration was analyzed by ex vivo microcomputerized X-ray tomography and histomorphometry of bones of BSP-deficient, OPN-deficient and wild-type mice. In all mouse strains, the cortical gap was bridged with woven bone within 2 weeks and no mineralized tissue was observed in the marrow. Within 3 weeks, lamellar cortical bone filled the gap. The amount and degree of mineralization of the woven bone was not affected by OPN deficiency, but cortical bone healing was delayed in BSP-deficient mice due to delayed mineralization. Gene expression studies showed a higher amount of BSP transcripts in the repair bone of OPN-deficient mice, suggesting a possible compensation of OPN function by BSP in OPN-null mice. Our data suggest that BSP, but not OPN, plays a role in primary bone formation and mineralization of newly formed bone during the process of cortical bone healing.
- Published
- 2010
22. Serum bone GLA-protein in growth hormone deficient children
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Pierre Chatelain, Luc Malaval, Graziela Bonne, and Pierre D. Delmas
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Osteocalcin ,Bone gla protein ,First year of life ,Growth hormone ,Growth velocity ,Internal medicine ,medicine ,Humans ,Orthopedics and Sports Medicine ,Bone formation ,Child ,Bone Development ,biology ,business.industry ,Calcium-Binding Proteins ,Infant ,Endocrinology ,Child, Preschool ,Growth Hormone ,Normal children ,biology.protein ,Female ,business ,Biomarkers ,GH Deficiency - Abstract
Serum bone GLA-protein (BGP), a sensitive and specific marker of bone formation, was measured in 54 normal children and in 50 children with growth disorders. In normal children, the pattern of variations of serum BGP with age was similar to the pattern of variations of the growth velocity. Mean serum BGP was very high during the first year of life (25.3 +/- 8.5 ng/ml), decreased to 14.8 +/- 2.2 ng/ml from 2 to 6 years, increased to 18.4 +/- 4.1 ng/ml from 7 to 10 years and to 18.8 +/- 6.5 ng/ml from 11 to 14 years. After puberty, mean sBGP decreased to 12.9 +/- 5.4 ng/ml from 15 to 18 years and to 6.5 +/- 1.4 ng/ml in young adults. In 32 patients with untreated growth hormone (GH) deficiency, mean sBGP was markedly lower than in age matched controls (6.8 +/- 4.4 ng/ml vs. 17.5 +/- 4.9 ng/ml, p less than .001). In 19 patients with GH deficiency who were undergoing treatment with human GH, sBGP was higher than in untreated patients (20.5 +/- 9.3 ng/ml vs. 6.8 +/- 4.4 ng/ml, p less than .001) and was not different from controls. Repeated measurements performed in 14 GH-deficient patients under chronic GH therapy showed that serum BGP: (1) increased in most patients during treatment (p less than .005); (2) was correlated with the duration of treatment (p less than .001); (3) decreased to pretreatment values after discontinuing therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 2009
23. Osteonectin is an α-granule component involved with thrombospondin in platelet aggregation
- Author
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Marie-Christine Morel, Josette Guichard, Marc Dechavanne, Pierre D. Delmas, Marie-Christine Trzeciak, Janine Breton-Gorius, Thomas Lecompte, Cecile Kaplan, Luc Malaval, and Philippe Clézardin
- Subjects
Adult ,Platelet Aggregation ,Endocrinology, Diabetes and Metabolism ,Blotting, Western ,Enzyme-Linked Immunosorbent Assay ,Platelet Membrane Glycoproteins ,Cytoplasmic Granules ,Gray platelet syndrome ,Immunoglobulin Fab Fragments ,medicine ,Humans ,Osteonectin ,Orthopedics and Sports Medicine ,Platelet ,Platelet activation ,Thrombospondins ,Thrombospondin ,biology ,Chemistry ,Thrombin ,Antibodies, Monoclonal ,Syndrome ,Immunogold labelling ,medicine.disease ,Microscopy, Electron ,Biochemistry ,Polyclonal antibodies ,biology.protein ,Female ,Blood Platelet Disorders ,Collagen - Abstract
We previously showed that thrombospondin, a major alpha-granule glycoprotein of human platelets, forms a specific complex with osteonectin, a phosphoglycoprotein originally described in bone that is also present in human platelets. The storage organelles and the function of osteonectin in platelets are still unknown. In this study, using electron microscopy in combination with immunogold staining, the major storage organelle for platelet-secreted proteins, the alpha-granules. Furthermore, osteonectin was qualitatively and quantitatively assessed by studying normal platelets and the platelets from a patient with gray platelet syndrome. Gray platelet syndrome is a rare congenital bleeding disorder characterized by a selective deficiency in morphologically recognizable platelet alpha-granules and in the alpha-granule secretory proteins. Binding of an iodinated antiosteonectin monoclonal antibody to gray platelet proteins transferred to nitrocellulose from SDS-polyacrylamide gels showed no band corresponding to osteonectin compared to control platelets. Using a polyclonal antiosteonectin antibody-based radioimmunoassay, gray platelets contained 0.2 +/- 0.03 ng osteonectin per 10(6) platelets, which is only 20% of the normal platelet content of osteonectin (0.93 +/- 0.16 ng per 10(6) platelets). Study of the localization of osteonectin to the surface of human platelets demonstrated that a radioiodinated antiosteonectin polyclonal antibody bound specifically to thrombin-stimulated platelets but not to resting platelets. Binding was concentration-dependent, saturable (1710 +/- 453 binding sites per platelet, Kd = 1 microM), and inhibited by an excess of cold antiosteonectin polyclonal antibody. No binding was observed on the surface of thrombin-stimulated gray platelets. To gain further insights into the role of osteonectin released from activated platelets, the effect of an antiosteonectin polyclonal antibody was tested on the aggregation of washed platelets. F(ab')2 fragments from the antiosteonectin polyclonal antibody inhibited in a dose-dependent manner the aggregation of collagen-stimulated, washed human platelets without affecting collagen-induced platelet serotonin release. To characterize the mechanism through which antiosteonectin F(ab')2 fragments inhibit platelet aggregation, the expression of endogenous thrombospondin (TSP) on the surface of thrombin-activated platelets was studied using 125I-labeled anti-TSP monoclonal antibody P10. The endogenous surface expression of TSP to thrombin-stimulated platelets was significantly inhibited in the presence of antiosteonectin F(ab')2 fragments (6286 +/- 2065 molecules of P10 per platelet) compared to 11,230 +/- 766 molecules of P10 per platelet in the presence of nonimmune F(ab')2 fragments.(ABSTRACT TRUNCATED AT 400 WORDS)
- Published
- 2009
24. Imaging and Quantitative Assessment of Long Bone Vascularization in the Adult Rat Using Microcomputed Tomography
- Author
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Jia Fei, Luc Malaval, Françoise Peyrin, Marie-Helene Lafage-Proust, Laurence Vico, Rayet, Béatrice, Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Synchrotron Radiation Facility (ESRF), INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Male ,Aging ,X-ray microtomography ,[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging ,Long bone ,Contrast Media ,Bone tissue ,0302 clinical medicine ,quantitative microcomputed tomography analysis ,rat ,Infusions, Intravenous ,0303 health sciences ,Bone decalcification ,medicine.diagnostic_test ,Age Factors ,Angiography ,medicine.anatomical_structure ,Hindlimb Suspension ,Radiographic Image Interpretation, Computer-Assisted ,Radiology ,Anatomy ,Perfusion ,Biotechnology ,medicine.medical_specialty ,bone marrow ,Histology ,030209 endocrinology & metabolism ,03 medical and health sciences ,Imaging, Three-Dimensional ,Sinusoid ,vascularization ,medicine ,Animals ,Rats, Wistar ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,business.industry ,Reproducibility of Results ,X-Ray Microtomography ,Capillaries ,Rats ,[SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging ,Venae Cavae ,Bone marrow ,Barium Sulfate ,business ,Nuclear medicine ,Synchrotrons ,tibia - Abstract
International audience; The objective of this study was to develop and validate a technique for both 3D imaging and quantification of the vascular network of bone tissue in the rat. Five month-old male Wistar rats were divided into tail-suspension (21 days) and control groups. Sixty percent barium sulfate solution was infused into the vena cava. The tibiae were evaluated in 2D and 3D before and after decalcification, using conventional microcompu-terized tomography (lCT) at 10 and 5 lm resolution and synchrotron radiation (SR) lCT. The perfusion technique and tomography exhibited excellent bone vasculature imaging. Significant positive correlations were observed between 2D histomorphometric and 3D lCT vascular parameters (P < 0.05). 3DlCT discriminated significant changes of vessel structures in unloading condition: vessel number decreased by 25%, (P < 0.005), vessel separation increased by 27%, P < 0.01. SRlCT could image sinusoid clusters in bone. lCT is an accurate and reproducible technique for 3D quantitative evaluation of long bone vascularisation in the rat. Anat Rec, 293:215-224
- Published
- 2009
25. Absence of bone sialoprotein (BSP) impairs cortical defect repair in mouse long bone
- Author
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Laurent Monfoulet, Jean-Michel Franconi, Thierry Fabre, Joëlle Amédée, Jane E. Aubin, Luc Malaval, Reine Bareille, Eric Thiaudière, Laurence Vico, Marie-Hélène Lafage-Proust, Laurent Pothuaud, Gérard Raffard, and Sylvain Miraux
- Subjects
musculoskeletal diseases ,Bone sialoprotein ,medicine.medical_specialty ,Histology ,Physiology ,Sialoglycoproteins ,Endocrinology, Diabetes and Metabolism ,Bone healing ,Bone and Bones ,Bone remodeling ,Mice ,fluids and secretions ,stomatognathic system ,Internal medicine ,Bone cell ,medicine ,Animals ,Integrin-Binding Sialoprotein ,Bone regeneration ,Bone mineral ,Wound Healing ,biology ,Chemistry ,Osteoid ,X-Ray Microtomography ,Anatomy ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Endocrinology ,biology.protein ,Cortical bone ,Bone Remodeling - Abstract
Matrix proteins of the SIBLING family interact with bone cells and with bone mineral and are thus in a key position to regulate bone development, remodeling and repair. Within this family, bone sialoprotein (BSP) is highly expressed by osteoblasts, hypertrophic chondrocytes and osteoclasts. We recently reported that mice lacking BSP (BSP−/−) have very low trabecular bone turnover. In the present study, we set up an experimental model of bone repair by drilling a 1 mm diameter hole in the cortical bone of femurs in both BSP−/− and +/+ mice. A non-invasive MRI imaging and bone quantification procedure was designed to follow bone regeneration, and these data were extended by μCT imaging and histomorphometry on undecalcified sections for analysis at cellular level. These combined approaches revealed that the repair process as reflected in defect-refilling in the cortical area was significantly delayed in BSP−/− mice compared to +/+ mice. Concomitantly, histomorphometry showed that formation, mineralization and remodeling of repair (primary) bone in the medulla were delayed in BSP−/− mice, with lower osteoid and osteoclast surfaces at day 15. In conclusion, the absence of BSP delays bone repair at least in part by impairing both new bone formation and osteoclast activity.
- Published
- 2009
26. Effects of whole body vibration on the skeleton and other organ systems in man and animal models: What we know and what we need to know
- Author
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Luc Malaval, Rhonda D. Prisby, Laurence Vico, Alain Belli, and Marie-Hélène Lafage-Proust
- Subjects
Aging ,medicine.medical_specialty ,Osteoporosis ,Population ,Vibration ,Biochemistry ,Bone and Bones ,Skeletal tissue ,Bone remodeling ,Mice ,Physical medicine and rehabilitation ,Need to know ,Internal medicine ,medicine ,Animals ,Humans ,Whole body vibration ,Nervous System Physiological Phenomena ,Muscle, Skeletal ,education ,Molecular Biology ,Organ system ,Aged ,Aged, 80 and over ,education.field_of_study ,business.industry ,Mechanism (biology) ,Middle Aged ,medicine.disease ,Biomechanical Phenomena ,Rats ,Endocrinology ,Neurology ,Body Composition ,Female ,Bone Remodeling ,business ,Biotechnology - Abstract
Previous investigations reported enhanced osseous parameters subsequent to administration of whole body vibration (WBV). While the efficacy of WBV continues to be explored, scientific inquiries should consider several key factors. Bone remodeling patterns differ according to age and hormonal status. Therefore, WBV protocols should be designed specifically for the subject population investigated. Further, administration of WBV to individuals at greatest risk for osteoporosis may elicit secondary physiological benefits (e.g., improved balance and mobility). Secondly, there is a paucity of data in the literature regarding the physiological modulation of WBV on other organ systems and tissues. Vibration-induced modulation of systemic hormones may provide a mechanism by which skeletal tissue is enhanced. Lastly, the most appropriate frequencies, durations, and amplitudes of vibration necessary for a beneficial response are unknown, and the type of vibratory signal (e.g., sinusoidal) is often not reported. This review summarizes the physiological responses of several organ systems in an attempt to link the global influence of WBV. Further, we report findings focused on subject populations that may benefit most from such a therapy (i.e., the elderly, postmenopausal women, etc.) in hopes of eliciting multidisciplinary scientific inquiries into this potentially therapeutic aid which presumably has global ramifications.
- Published
- 2008
27. Ex VivoBone Formation in Bovine Trabecular Bone Cultured in a Dynamic 3D Bioreactor Is Enhanced by Compressive Mechanical Strain
- Author
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Valentin David, Alain Guignandon, Aline Martin, Luc Malaval, Marie-Hélène Lafage-Proust, Aline Rattner, Val Mann, Brendon Noble, David B. Jones, and Laurence Vico
- Subjects
General Engineering - Published
- 2008
28. Plasticity of osteoprogenitor cells
- Author
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Thierry Thomas, Aline Rattner, Marie-Hélène Lafage-Proust, Laurence Vico, Luc Malaval, and Alain Guignandon
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Stromal cell ,Cellular differentiation ,Clinical uses of mesenchymal stem cells ,Bone Marrow Cells ,Biology ,Xenobiotics ,Weight-Bearing ,Chondrocytes ,Rheumatology ,Adipocytes ,medicine ,Animals ,Humans ,Cell Lineage ,Progenitor cell ,Osteoblasts ,Mesenchymal stem cell ,Cell Differentiation ,Cell biology ,Endothelial stem cell ,Adult Stem Cells ,medicine.anatomical_structure ,Pharmaceutical Preparations ,Immunology ,Bone marrow ,Stromal Cells ,Stem cell - Abstract
Plasticity is the ability to give rise to cell types whose phenotype is different from that of the source tissue. Osteoblasts originate in progenitors located in the bone marrow or around blood vessels. Marrow stromal cells can differentiate into adipocytes, in part at the expense of osteoblasts. The osteoblast–adipocyte balance is influenced by systemic factors, chiefly hormones, and local factors in the microenvironment, as well as by mechanical loads, which induce or suppress the activity of transcription factors crucial to the differentiation of each cell type. New insights into the molecular mechanisms involved in controlling the osteoblast–adipocyte balance are unlocking doors to a vast array of innovative treatment strategies.
- Published
- 2007
29. Plasticité des cellules ostéoprogénitrices
- Author
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Alain Guignandon, Thierry Thomas, Luc Malaval, Laurence Vico, Aline Rattner, and Marie-Hélène Lafage-Proust
- Subjects
Stromal cell ,Rheumatology ,Cellular differentiation ,Biology ,Stem cell ,Cellules souches ,Molecular biology - Abstract
Resume La plasticite cellulaire est la capacite de certaines cellules a se differencier en types cellulaires dont le phenotype est different, voire sans rapport avec celui de leur tissu d'origine. Les osteoblastes proviennent de la differenciation de progeniteurs qui sont situes dans la moelle osseuse ou a la peripherie des vaisseaux. Les cellules stromales de moelle peuvent se differencier, entre autres, en adipocytes en partie aux depens des osteoblastes. Des facteurs systemiques le plus souvent hormonaux, ou locaux, apportes par le microenvironnement et les contraintes mecaniques sont capables de moduler la balance osteoblaste/ adipocytes en induisant ou reprimant l'activite de facteurs de transcription necessaires a leur differenciation. Une meilleure connaissance des bases moleculaires de ce controle ouvre de nombreuses perspectives therapeutiques.
- Published
- 2007
30. Opposite Effects of Leptin on Bone Metabolism: A Dose-Dependent Balance Related to Energy Intake and Insulin-Like Growth Factor-I Pathway
- Author
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Valentin David, Thierry Thomas, Laurence Vico, Luc Malaval, Aline Martin, and Marie-Hélène Lafage-Proust
- Subjects
Leptin ,medicine.medical_specialty ,medicine.medical_treatment ,Adipokine ,Bone and Bones ,Bone resorption ,Bone remodeling ,Insulin-like growth factor ,Endocrinology ,Bone Density ,Osteogenesis ,Internal medicine ,Adipocytes ,medicine ,Animals ,Femur ,Insulin-Like Growth Factor I ,Rats, Wistar ,Dose-Response Relationship, Drug ,Tibia ,Chemistry ,Body Weight ,digestive, oral, and skin physiology ,Metabolism ,Rats ,Dose–response relationship ,Female ,Energy Intake ,Tomography, X-Ray Computed ,hormones, hormone substitutes, and hormone antagonists ,Signal Transduction ,Hormone - Abstract
Published data describing leptin effects on bone are at variance with both positive and negative consequences reported. These findings are consistent with a bimodal threshold response to serum leptin levels. To test this theory, two groups of female rats (tail-suspended and unsuspended) were treated with ip leptin at two different doses or vehicle for 14 d. In tail-suspended rats, low-dose leptin compensated the decrease in serum leptin levels observed with suspension and was able to prevent the induced bone loss at both the trabecular and cortical level (assessed by three-dimensional microtomography). In contrast, high-dose leptin inhibited femoral bone growth and reduced bone mass by decreasing bone formation rate and increasing bone resorption in both tail-suspended and unsuspended groups. High- and low-dose leptin administration resulted in a reduced medullar adipocytic volume in all groups. High-dose leptin (but not low) induced a decrease in body-weight abdominal fat mass and serum IGF-I levels. Thus, the observed bone changes at high-dose leptin are at least partly mediated by a leptin-induced energy imbalance. In conclusion, a balance between negative and positive leptin effects on bone is dependent on a bimodal threshold that is triggered by leptin serum concentration. Also, the negative effects of high leptin levels are likely induced by reduced energy intake and related hormonal changes. The respective part of each pathway will be unraveled by additional studies.
- Published
- 2007
31. Mechanical Loading Down-Regulates Peroxisome Proliferator-Activated Receptor γ in Bone Marrow Stromal Cells and Favors Osteoblastogenesis at the Expense of Adipogenesis
- Author
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David Jones, Valentin David, Alain Guignandon, Aline Martin, Laurence Vico, Sylvie Peyroche, Marie-Hélène Lafage-Proust, Luc Malaval, Tissu Osseux et Contraintes Mecaniques (LBTO), Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Contraintes mécaniques et tissu osseux, Experimental orthopaedics and biomechanics, Université de Marburg, and Vico, Laurence
- Subjects
Male ,Peroxisome proliferator-activated receptor ,Core Binding Factor Alpha 1 Subunit ,MESH: Physical Conditioning, Animal ,MESH: Down-Regulation ,chemistry.chemical_compound ,Endocrinology ,Adipocyte ,Adipocytes ,MESH: Animals ,Cell Line, Transformed ,chemistry.chemical_classification ,[SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,MESH: Stress, Mechanical ,Adipogenesis ,MESH: Bone Marrow Cells ,Cell Differentiation ,Osteoblast ,MESH: Core Binding Factor Alpha 1 Subunit ,RUNX2 ,MESH: Cattle ,medicine.anatomical_structure ,[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,MESH: Cell Differentiation ,medicine.medical_specialty ,Stromal cell ,MESH: Rats ,Down-Regulation ,Bone Marrow Cells ,Biology ,MESH: Tibia ,Physical Conditioning, Animal ,Internal medicine ,medicine ,Animals ,MESH: Cell Line, Transformed ,Rats, Wistar ,MESH: Adipocytes ,MESH: Osteoblasts ,Osteoblasts ,Tibia ,Activator (genetics) ,Mesenchymal Stem Cells ,MESH: Rats, Wistar ,MESH: Male ,Rats ,PPAR gamma ,MESH: Mesenchymal Stem Cells ,MESH: PPAR gamma ,chemistry ,Cattle ,Stress, Mechanical ,Bone marrow ,MESH: Stromal Cells ,Stromal Cells ,MESH: Adipogenesis - Abstract
Because a lack of mechanical information favors the development of adipocytes at the expense of osteoblasts, we hypothesized that the peroxisome proliferator-activated receptor gamma (PPARgamma)-dependent balance between osteoblasts and adipocytes is affected by mechanical stimuli. We tested the robustness of this hypothesis in in vivo rodent osteogenic exercise, in vitro cyclic loading of cancellous haversian bone samples, and cyclic stretching of primary stromal and C3H10T1/2 cells. We found that running rats exhibit a decreased marrow fat volume associated with an increased bone formation, presumably through recruitment of osteoprogenitors. In the tissue culture model and primary stromal cells, cyclic loading induced higher Runx2 and lower PPARgamma2 protein levels. Given the proadipocytic and antiosteoblastic activities of PPARgamma, we studied the effects of cyclic stretching in C3H10T1/2 cells, treated either with the PPARgamma activator, Rosiglitazone, or with GW9662, a potent antagonist of PPARgamma. We found, through both cytochemistry and analysis of lineage marker expression, that under Roziglitazone cyclic stretch partially overcomes the induction of adipogenesis and is still able to favor osteoblast differentiation. Conversely, cyclic stretch has additive effects with GW9662 in inducing osteoblastogenesis. In conclusion, we provide evidence that mechanical stimuli are potential PPARgamma modulators counteracting adipocyte differentiation and inhibition of osteoblastogenesis.
- Published
- 2007
32. Absence of mechanical loading in utero influences bone mass and architecture but not innervation in Myod-Myf5-deficient mice
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Valentin David, Cédric Gomez, Nicola M. Peet, Luc Malaval, Timothy M. Skerry, Chantal Chenu, and Laurence Vico
- Subjects
medicine.medical_specialty ,Histology ,Genotype ,Movement ,Osteoclasts ,Breeding ,Biology ,MyoD ,Nervous System ,Bone and Bones ,Bone remodeling ,Fetal Development ,Mice ,Calcification, Physiologic ,Internal medicine ,medicine ,Animals ,Muscle, Skeletal ,Molecular Biology ,Endochondral ossification ,Ecology, Evolution, Behavior and Systematics ,MyoD Protein ,Mice, Knockout ,Fetus ,Bone Development ,Skeletal muscle ,Original Articles ,Cell Biology ,Immunohistochemistry ,Microradiography ,Biomechanical Phenomena ,Mice, Inbred C57BL ,Endocrinology ,medicine.anatomical_structure ,In utero ,Female ,MYF5 ,Bone Remodeling ,Myogenic Regulatory Factor 5 ,Anatomy ,Tomography, X-Ray Computed ,Biomarkers ,Developmental Biology - Abstract
Although the responses of bone to increased loading or exercise have been studied in detail, our understanding of the effects of decreased usage of the skeleton has been limited by the scarcity of suitable models. Such models should ideally not affect bone innervation, which appears to be a mediator of physiological responses of bone to unloading. MyoD-/-/Myf5-/- (dd/ff) mice lack skeletal muscle, so the fetuses develop without any active movement in utero and die soon after birth. We used micro-compter tomography and histology to analyse their bone development and structure during endochondral ossification in parallel with the establishment of bone innervation. Long bones from mutant mice were found to be profoundly different from controls, with shorter mineralized zones and less mineralization. They lacked many characteristics of adult bones - curvatures, changes in shaft diameter and traction epiphyses where muscles originate or insert - that were evident in the controls. Histologically, dd/ff mice showed the same degree of endochondral development as wild-type animals, but presented many more osteoclasts in the newly layed bone. Innervation and the expression pattern of semaphorin-3A signalling molecules were not disturbed in the mutants. Overall, we have found no evidence for a major defect of development in dd/ff mice, and specifically no alteration or delay in endochondral ossification and bone innervation. The altered morphological features of dd/ff mice and the increased bone resorption show the role of muscle activity in bone shaping and the consequences of bone unloading.
- Published
- 2007
33. The role of the SIBLING, Bone Sialoprotein in skeletal biology - Contribution of mouse experimental genetics
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Renata Neves Granito, Laura Juignet, Wafa Bouleftour, Luc Malaval, Laurence Vico, Marie-Hélène Lafage-Proust, Guenaelle Bouet, Arnaud Vanden-Bossche, Norbert Laroche, and Jane E. Aubin
- Subjects
0301 basic medicine ,Bone sialoprotein ,medicine.medical_specialty ,Osteoclasts ,Bone and Bones ,03 medical and health sciences ,Mice ,fluids and secretions ,0302 clinical medicine ,Calcification, Physiologic ,stomatognathic system ,Osteoclast ,Internal medicine ,medicine ,Integrin-Binding Sialoprotein ,Animals ,Humans ,Osteopontin ,Molecular Biology ,SIBLING proteins ,Gene knockout ,Mice, Knockout ,Osteoblasts ,biology ,Osteoblast ,Cell Differentiation ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,030220 oncology & carcinogenesis ,Knockout mouse ,biology.protein ,Tooth - Abstract
Bone Sialoprotein (BSP) is a member of the "Small Integrin-Binding Ligand N-linked Glycoproteins" (SIBLING) extracellular matrix protein family of mineralized tissues. BSP has been less studied than other SIBLING proteins such as Osteopontin (OPN), which is coexpressed with it in several skeletal cell types. Here we review the contribution of genetically engineered mice (BSP gene knockout and overexpression) to the understanding of the role of BSP in the bone organ. The studies made so far highlight the role of BSP in skeletal mineralization, as well as its importance for proper osteoblast and osteoclast differentiation and activity, most prominently in primary/repair bone. The absence of BSP also affects the local environment of the bone tissue, in particular hematopoiesis and vascularization. Interestingly, lack of BSP induces an overexpression of OPN, and the cognate protein could be responsible for some aspects of the BSP gene knockout skeletal phenotype, while replacing BSP for some of its functions. Such interplay between the partly overlapping functions of SIBLING proteins, as well as the network of cross-regulations in which they are involved should now be the focus of further work.
- Published
- 2015
34. A review on the coupling of cooling, desalination and solar photovoltaic systems
- Author
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Anthony Szymczyk, Thierry Maré, Anthony Delahaye, Paul Byrne, Ousmane Sow, Yacine Ait Oumeziane, Laurent Serres, Jamel Orfi, Jean-Luc Malaval, Hervé Guéguen, Daniel Mugnier, Patrick Loulergue, Laurence Fournaison, Romain Bourdais, Laboratoire de Génie Civil et Génie Mécanique (LGCGM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), TECSOL, NKE instrumentation, Institut d'Electronique et de Télécommunications de Rennes (IETR), Centre National de la Recherche Scientifique (CNRS)-Ecole Supérieure d'Electricité - SUPELEC (FRANCE)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), King Saud University [Riyadh] (KSU), Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Rennes-Université de Rennes 1 (UR1), entreprise, Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-SUPELEC-Centre National de la Recherche Scientifique (CNRS), King Saud University - KSU (SAUDI ARABIA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Supérieure d'Electricité - SUPELEC (FRANCE)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Engineering ,Passive cooling ,020209 energy ,Low-temperature thermal desalination ,02 engineering and technology ,Geothermal desalination ,7. Clean energy ,Desalination ,Solar air conditioning ,020401 chemical engineering ,Solar energy ,0202 electrical engineering, electronic engineering, information engineering ,Water cooling ,0204 chemical engineering ,Process engineering ,Waste management ,Renewable Energy, Sustainability and the Environment ,business.industry ,6. Clean water ,[SPI.GCIV]Engineering Sciences [physics]/Civil Engineering ,13. Climate action ,Solar humidification ,[PHYS.MECA.THER]Physics [physics]/Mechanics [physics]/Thermics [physics.class-ph] ,business ,Cooling - Abstract
[Departement_IRSTEA]Ecotechnologies [TR1_IRSTEA]SPEE; International audience; Single cooling and desalination technologies require a high amount of energy to produce cooling and fresh water, respectively. Coupling these systems seems to be attractive not only to reduce their energy consumption rates and to gain more flexibility in operation but also for environmental considerations. Besides, using solar energy to drive these coupled systems appears also interesting. The major increases in cooling and desalination demands occur in locations where solar energy is abundant. This article reviews the latest research works on systems able to carry out cooling and/or desalination using solar energy. The ability of coupling desalination technologies to cooling systems is investigated. A heat pump can produce cooling energy at the evaporator and heat at the condenser for a membrane distillation unit. An ice slurry process can operate with sea water. It freezes only pure water that can be separated from the liquid. A comparison of these systems is made. Membrane distillation (MD) and ice slurry systems must improve to be as efficient as standard technologies. An intelligent energy and water production management will have to be developed to control the operation of a system coupling ice slurry, MD and solar photovoltaic energy.
- Published
- 2015
35. High-acceleration whole body vibration stimulates cortical bone accrual and increases bone mineral content in growing mice
- Author
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Arnaud Vanden-Bossche, Norbert Laroche, Luc Malaval, Vasily Gnyubkin, Alain Guignandon, and Laurence Vico
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Bone density ,Acceleration ,Biomedical Engineering ,Biophysics ,030209 endocrinology & metabolism ,Vibration ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Bone Density ,Osteogenesis ,Internal medicine ,medicine ,Cortical Bone ,Animals ,Orthopedics and Sports Medicine ,Femur ,Bone growth ,Bone mineral ,business.industry ,Rehabilitation ,X-Ray Microtomography ,medicine.disease ,Spine ,Osteopenia ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Osteocyte ,Sclerostin ,Cortical bone ,business - Abstract
Whole body vibration (WBV) is a promising tool for counteracting bone loss. Most WBV studies on animals have been performed at acceleration
- Published
- 2015
36. Pharmacological inhibition of Dock5 prevents osteolysis by affecting osteoclast podosome organization while preserving bone formation
- Author
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Jacqueline Cherfils, Anne Blangy, Mahel Zeghouf, Muriel Busson, Christian Richard, Virginie Vives, Anne-Gaëlle Planson, Gaelle Cres, Luc Malaval, Yann Ferrandez, Centre de recherches de biochimie macromoléculaire (CRBM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-IFR122-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire d'Enzymologie et Biochimie Structurales, Centre National de la Recherche Scientifique (CNRS), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR: ANR grant,ANR-2011-BLAN-006 to A.B., Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Laboratoire d'Enzymologie et Biochimie Structurales (LEBS), Biologie intégrative du tissu osseux, and Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Male ,musculoskeletal diseases ,Osteolysis ,Podosome ,[SDV]Life Sciences [q-bio] ,Osteoporosis ,PARATHYROID-HORMONE ,PATHOGENESIS ,Osteoclasts ,General Physics and Astronomy ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,OSTEOPOROSIS ,General Biochemistry, Genetics and Molecular Biology ,Bone resorption ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Osteogenesis ,Osteoclast ,medicine ,Animals ,Guanine Nucleotide Exchange Factors ,ALENDRONATE ,030304 developmental biology ,Sulfonamides ,0303 health sciences ,Multidisciplinary ,biology ,Chemistry ,Arthritis ,Dock5 ,Bone metastasis ,Osteoblast ,General Chemistry ,medicine.disease ,CHEMOKINE ,Mice, Inbred C57BL ,[SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics ,MODEL ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,biology.protein ,Female ,SIGNALING PATHWAY - Abstract
International audience; Osteoporosis is caused by excessive activity of bone-degrading osteoclasts over bone-forming osteoblast. Standard antiosteolytic treatments inhibit bone resorption by inducing osteoclast loss, with the adverse effect of hindering also bone formation. Formation of the osteoclast sealing zone requires Dock5, a guanine nucleotide exchange factor for the small GTPase Rac, and C21, a chemical inhibitor of Dock5, decreases bone resorption by cultured osteoclasts. Here we show that C21 directly inhibits the exchange activity of Dock5 and disrupts osteoclast podosome organization. Remarkably, C21 administration protects mice against bone degradation in models recapitulating major osteolytic diseases: menopause, rheumatoid arthritis and bone metastasis. Furthermore, C21 administration does not affect bone formation and is not toxic. Our results validate the pharmacological inhibition of Dock5 as a novel therapeutic route for fighting osteolytic diseases while preserving bone formation.
- Published
- 2015
37. The Impairment of Osteogenesis in Bone Sialoprotein (BSP) Knockout Calvaria Cell Cultures Is Cell Density Dependent
- Author
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Arnaud Vanden-Bossche, David Marchat, Guenaelle Bouet, Marie Thérèse Linossier, Wafa Bouleftour, Luc Malaval, Laura Juignet, Mireille Thomas, Jane E. Aubin, Laurence Vico, Biologie intégrative du tissu osseux, Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Molecular and Medical Genetics, University of Toronto, Ingénierie des Biomatériaux et des Particules Inhalées (BIOPI-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-CIS
- Subjects
Bone sialoprotein ,Male ,medicine.medical_specialty ,Bone density ,Science ,[SDV]Life Sciences [q-bio] ,Calvaria ,Apoptosis ,Bone Marrow Cells ,Bone remodeling ,Cathepsin B ,03 medical and health sciences ,Mice ,0302 clinical medicine ,fluids and secretions ,stomatognathic system ,Osteogenesis ,Internal medicine ,Bone cell ,medicine ,Animals ,[SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering ,Osteopontin ,SIBLING proteins ,Cells, Cultured ,030304 developmental biology ,Cell Proliferation ,Mice, Knockout ,0303 health sciences ,Multidisciplinary ,biology ,Skull ,Osteoblast ,Cell Differentiation ,PHEX Phosphate Regulating Neutral Endopeptidase ,Coculture Techniques ,Cell biology ,medicine.anatomical_structure ,Endocrinology ,030220 oncology & carcinogenesis ,biology.protein ,Medicine ,Female ,Research Article - Abstract
International audience; Bone sialoprotein (BSP) belongs to the "small integrin-binding ligand N-linked glycoprotein" (SIBLING) family, whose members interact with bone cells and bone mineral. BSP is strongly expressed in bone and we previously showed that BSP knockout (BSP-/-) mice have a higher bone mass than wild type (BSP+/+) littermates, with lower bone remodelling. Because baseline bone formation activity is constitutively lower in BSP-/-mice, we studied the impact of the absence of BSP on in vitro osteogenesis in mouse calvaria cell (MCC) cultures. MCC BSP-/-cultures exhibit fewer fibroblast (CFU-F), preosteoblast (CFU-ALP) and osteoblast colonies (bone nodules) than wild type, indicative of a lower number of osteopro-genitors. No mineralized colonies were observed in BSP-/-cultures, along with little/no expression of either osteogenic markers or SIBLING proteins MEPE or DMP1. Osteopontin (OPN) is the only SIBLING expressed in standard density BSP-/-culture, at higher levels than in wild type in early culture times. At higher plating density, the effects of the absence of BSP were partly rescued, with resumed expression of osteoblast markers and cognate SIBLING proteins, and mineralization of the mutant cultures. OPN expression and amount are further increased in high density BSP-/-cultures, while PHEX and CatB expression are differentiatlly regulated in a manner that may favor mineralization. Altogether, we found that BSP regulates mouse calvaria osteoblast cell clonogenicity, differentiation and activity in vitro in a cell density dependent manner, consistent with the effective skeletogenesis but the low levels of bone formation observed in vivo. The BSP knockout bone microenviron-ment may alter the proliferation/cell fate of early osteoprogenitors.
- Published
- 2015
38. Absence of bone sialoprotein (BSP) alters profoundly hematopoiesis and upregulates osteopontin
- Author
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Renata Neves, Granito, Wafa, Bouleftour, Odile, Sabido, Chloé, Lescale, Mireille, Thomas, Jane E, Aubin, Michèle, Goodhardt, Laurence, Vico, and Luc, Malaval
- Subjects
Transcriptional Activation ,Mice ,Bone Marrow ,Osteogenesis ,Animals ,Integrin-Binding Sialoprotein ,Mice, Nude ,Osteopontin ,Bone and Bones ,Hematopoiesis ,Up-Regulation - Abstract
Matrix proteins of the SIBLING family interact with bone cells, extracellular matrix and mineral and are thus in a key position to regulate the microenvironment of the bone tissue, including its hematopoietic component. In this respect, osteopontin (OPN) has been implicated in the hematopoietic stem cell (HSC) niche as negative regulator of the HSC function. We investigated the impact on hematopoietic regulation of the absence of the cognate bone sialoprotein (BSP). BSP knockout (-/-) mice display increased bone marrow cellularity, and an altered commitment of hematopoietic precursors to myeloid lineages, leading in particular to an increased frequency of monocyte/macrophage cells. The B cell pool is increased in -/- bone marrow, and its composition is shifted toward more mature lymphocyte stages. BSP-null mice display a decreased HSC fraction among LSK cells and a higher percentage of more committed progenitors as compared to +/+. The fraction of proliferating LSK progenitors is higher in -/- mice, and after PTH treatment the mutant HSC pool is lower than in +/+. Strikingly, circulating levels of OPN as well as its expression in the bone tissue are much higher in the -/-. Thus, a BSP-null bone microenvironment affects the hematopoietic system both quantitatively and qualitatively, in a manner in part opposite to the OPN knockout, suggesting that the effects might in part reflect the higher OPN expression in the absence of BSP.
- Published
- 2014
39. Expression of leukemia inhibitory factor (LIF)/interleukin-6 family cytokines and receptors during in vitro osteogenesis: differential regulation by dexamethasone and LIF
- Author
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Fina Liu, Jane E. Aubin, and Luc Malaval
- Subjects
endocrine system ,medicine.medical_specialty ,Histology ,Leukemia Inhibitory Factor Receptor alpha Subunit ,Receptors, OSM-LIF ,Physiology ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Cellular differentiation ,Leukemia inhibitory factor receptor ,Biology ,Leukemia Inhibitory Factor ,Dexamethasone ,Fetus ,Osteogenesis ,Internal medicine ,medicine ,Animals ,Rats, Wistar ,Receptors, Cytokine ,Receptor ,Cells, Cultured ,Lymphokines ,Dose-Response Relationship, Drug ,Interleukin-6 ,Osteoblast ,Glycoprotein 130 ,Receptors, Interleukin-6 ,Growth Inhibitors ,Rats ,Cell biology ,Cytokine ,medicine.anatomical_structure ,Endocrinology ,Gene Expression Regulation ,Cell culture ,Multigene Family ,Cytokines ,Leukemia inhibitory factor ,hormones, hormone substitutes, and hormone antagonists - Abstract
The leukemia inhibitory factor/interleukin-6 (LIF/IL-6) family of cytokines is known to play a major role in bone physiology. Although much work has focused on the regulation of bone resorption by IL-6 and related cytokines, their effects on osteoblast development and bone formation have not been as well studied. Previously, we reported that LIF inhibits, in a non-IL-6-dependent manner, osteoblast differentiation and bone nodule formation in the rat calvaria (RC) model, an effect that is antagonized by dexamethasone (Dex). The culture time-sensitive window suggested that LIF targets late preosteoblasts or early osteoblasts, and that this stage-specific effect coincided with a period of low endogenous production of LIF and IL-6. To detect potential crosstalk between members of this family, we have extended these observations by assessing the expression levels of other LIF/IL-6 cytokines (CNTF, OSM, IL-11, CT-1) and their receptors in the same RC cell model treated with or without LIF or Dex. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that IL-11 and its receptor, CNTF and its receptor, LIFR, and gp130 were constitutively expressed throughout the culture period. Expression of CT-1 and OSM increased with culture time — that is, with osteoblast differentiation — whereas the specific receptor for OSM (OSMR) was highly expressed at early timepoints and either plateaued or decreased thereafter. Continuous treatment with Dex (10 −8 mol/L) inhibited the endogenous production of IL-6, LIF, OSM, IL-11R, and OSMR, but had no detectable effect on the expression of IL-11, CT-1, CNTF, CNTFR, LIFR, or gp130. Finally, treatment with exogenously added LIF stimulated IL-6, LIF, LIFR, and OSMR, but had no other detectable effects. These data indicate that multiple members of the LIF/IL-6 family and their receptors are expressed in RC cell cultures, and are differentially regulated by Dex and LIF, suggesting that these cytokines play a complex and interdependent role, further modulated by glucocorticoid levels, in osteoprogenitor differentiation and bone nodule formation.
- Published
- 2002
40. Investigation of osteocalcin, osteonectin, and dentin sialophosphoprotein in developing human teeth
- Author
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J Nydegger, Ariane Berdal, Luc Malaval, M Peuchmaur, James P. Simmer, Petros Papagerakis, Mary MacDougall, and M. Mesbah
- Subjects
Adult ,Mineralized tissues ,Pathology ,medicine.medical_specialty ,Histology ,Physiology ,Sialoglycoproteins ,Endocrinology, Diabetes and Metabolism ,Osteocalcin ,Fetus ,stomatognathic system ,Dentin sialophosphoprotein ,medicine ,Dentin ,Humans ,Osteonectin ,RNA, Messenger ,Cementum ,Protein Precursors ,Child ,Cells, Cultured ,Extracellular Matrix Proteins ,Odontoblasts ,Chemistry ,Infant, Newborn ,Gene Expression Regulation, Developmental ,Amelogenesis ,Phosphoproteins ,Cell biology ,stomatognathic diseases ,medicine.anatomical_structure ,Odontoblast ,Dentinogenesis ,Ameloblast ,Tooth - Abstract
Biochemical investigations in rodents have shown that numerous mineralized matrix proteins share expression in bone, dentin, and cementum. Little information is available regarding the expression pattern of these proteins in human tissues, particularly during tooth formation. The aim of this study was to identify the expression pattern of the two major noncollagenous proteins of bone and dentin, osteocalcin (OC) and osteonectin (ON), in comparison to the dentin-specific protein, dentin sialophosphoprotein (DSPP). Mandibles from fetuses (5-26 weeks), neonate autopsies, forming teeth from 10-12-year-old patients, third molars extracted for orthodontic reasons, and bone tumors were collected with approval from the National Ethics Committee. Human OC, ON, and DSPP mRNAs were detected by reverse transcription-polymerase chain reaction (RT-PCR) in fetal mandibles (5-11 weeks) and in primary cell cultures of dental pulp. In addition, OC, ON, and DSPP proteins were localized in forming human mineralized tissues using immunohistochemistry. In vivo, DSPP expression was associated with tooth terminal epithelial-mesenchymal interaction events, amelogenesis and dentinogenesis. Transient DSPP expression was seen in the presecretory ameloblasts with continuous expression in the odontoblasts. In contrast, both osteoblasts and odontoblasts showed a temporal gap between OC and ON expression in early development. ON was expressed in the initial stages of cytodifferentiation, whereas OC was expressed only during the later stages, especially in the teeth. At the maturation stage of enamel formation, both proteins were detected in odontoblasts and their processes within the extracellular matrix. In contrast to bone, OC was not localized extracellularly within the collagen-rich dentin matrix (predentin or intertubular dentin), but was found in the mature enamel. ON was present mostly in the nonmineralized predentin. These results demonstrate for the first time that both OC and ON are produced by human odontoblasts and determine the expression pattern of DSPP in human teeth, and suggest that OC and ON move inside the canalicule via odontoblast cell processes becoming localized to specific extracellular compartments during dentin and enamel formation. These distinct extracellular patterns may be related to the nature of DSPP, OC, and ON interactions with other matrix-specific macromolecules (i.e., amelogenin, dentin matrix protein-1) and/or to the polarized organization of odontoblast secretion as compared with osteoblasts.
- Published
- 2002
41. In vitro three-dimensional bone tissue models: from cells to controlled and dynamic environment
- Author
-
Guenaelle Bouet, David Marchat, Luc Malaval, Laurence Vico, and Magali Cruel
- Subjects
Scaffold ,Computer science ,Cells ,Biomedical Engineering ,Bioengineering ,02 engineering and technology ,Computational biology ,Bone tissue ,Biochemistry ,Models, Biological ,Bone and Bones ,Biomaterials ,03 medical and health sciences ,Bioreactors ,Imaging, Three-Dimensional ,In vivo ,Bone cell ,medicine ,Animals ,Humans ,Bone biology ,030304 developmental biology ,0303 health sciences ,Tissue Scaffolds ,021001 nanoscience & nanotechnology ,Perfusion bioreactor ,In vitro ,medicine.anatomical_structure ,Cell culture ,0210 nano-technology ,Biomedical engineering - Abstract
Most of our knowledge of bone cell physiology is derived from experiments carried out in vitro on polystyrene substrates. However, these traditional monolayer cell cultures do not reproduce the complex and dynamic three-dimensional (3D) environment experienced by cells in vivo. Thus, there is a growing interest in the use of 3D culture systems as tools for understanding bone biology. These in-vitro-engineered systems, less complex than in vivo models, should ultimately recapitulate and control the main biophysical, biochemical, and biomechanical cues that define the in vivo bone environment, while allowing their monitoring. This review focuses on state-of-the-art and the current advances in the development of 3D culture systems for bone biology research. It describes more specifically advantages related to the use of such systems, and details main characteristics and challenges associated with its three main components, that is, scaffold, cells, and perfusion bioreactor systems. Finally, future challenges for noninvasive imaging technologies are addressed.
- Published
- 2014
42. Blocking the expression of both bone sialoprotein (BSP) and osteopontin (OPN) impairs the anabolic action of PTH in mouse calvaria bone
- Author
-
Wafa, Bouleftour, Guenaelle, Bouet, Renata Neves, Granito, Mireille, Thomas, Marie-Thérèse, Linossier, Arnaud, Vanden-Bossche, Jane E, Aubin, Marie-Hélène, Lafage-Proust, Laurence, Vico, and Luc, Malaval
- Subjects
Mice ,Osteogenesis ,Parathyroid Hormone ,Skull ,Animals ,Gene Expression Regulation, Developmental ,Integrin-Binding Sialoprotein ,Osteopontin ,RNA, Messenger ,Cells, Cultured - Abstract
Osteopontin (OPN) and bone sialoprotein (BSP) are coexpressed in osteoblasts and osteoclasts, and display overlapping properties. We used daily injection of parathyroid hormone 1-84 (iPTH) over the calvaria of BSP knockout (-/-) mice to investigate further their functional specificity and redundancy. iPTH stimulated bone formation in both +/+ and -/- mice, increasing to the same degree periosteum, osteoid and total bone thickness. Expression of OPN, osterix, osteocalcin (OCN) and DMP1 was also increased by iPTH in both genotypes. In contrast to +/+, calvaria cell cultures from -/- mice revealed few osteoblast colonies, no mineralization and little expression of OCN, MEPE or DMP1. In contrast, OPN levels were 5× higher in -/- versus +/+ cultures. iPTH increased alkaline phosphatase (ALP) activity in cell cultures of both genotypes, with higher OCN and the induction of mineralization in -/- cultures. siRNA blocking of OPN expression did not alter the anabolic action of the hormone in BSP +/+ calvaria, while it blunted iPTH effects in -/- mice, reduced to a modest increase in periosteum thickness. In -/- (not +/+) cell cultures, siOPN blocked the stimulation by iPTH of ALP activity and OCN expression, as well as the induction of mineralization. Thus, full expression of either OPN or BSP is necessary for the anabolic effect of PTH at least in the ectopic calvaria injection model. This suggests that OPN may compensate for the lack of BSP in the response to this hormonal challenge, and provides evidence of functional overlap between these cognate proteins.
- Published
- 2014
43. Biphasic effects of leukemia inhibitory factor on osteoblastic differentiation
- Author
-
Jane E. Aubin and Luc Malaval
- Subjects
Male ,Stromal cell ,Leukemia Inhibitory Factor Receptor alpha Subunit ,Receptors, OSM-LIF ,Cellular differentiation ,Cell ,Bone Marrow Cells ,Cell Count ,Biology ,Leukemia Inhibitory Factor ,Biochemistry ,Bone remodeling ,medicine ,Animals ,Rats, Wistar ,Receptors, Cytokine ,Molecular Biology ,Lymphokines ,Osteoblasts ,Interleukin-6 ,Reverse Transcriptase Polymerase Chain Reaction ,Cell growth ,Cell Differentiation ,Osteoblast ,Cell Biology ,Growth Inhibitors ,Rats ,Cell biology ,medicine.anatomical_structure ,Cell culture ,embryonic structures ,Immunology ,Leukemia inhibitory factor - Abstract
Leukemia inhibitory factor (LIF) is a cytokine produced by multiple cell types including osteoblasts and which is active on bone metabolism. We have previously shown that in a bone nodule forming in vitro model of osteogenesis, the fetal rat calvaria (RC) cell model, LIF inhibits osteoblast differentiation, acting on late osteoprogenitors and/or early osteoblasts. These results are in contrast to in vivo experiments, in which LIF has been found to increase bone formation. To resolve this discrepancy, we have tested the effect of LIF on rat bone marrow (RBM) stromal cell cultures, an in vitro model encompassing earlier osteoprogenitor stages. LIF inhibited cell growth in early, proliferating RBM cultures, but increased the culture saturation density. The effect of LIF on bone nodule formation in this model was cell density dependent and biphasic. Continuous treatment with LIF reduced the number of bone nodules present in confluent, more mature cultures, and the inhibitory effect was strongest when cells were plated at higher cell density than lower. In contrast, during the early stages of RBM culture, nodule numbers were higher in LIF-treated dishes than in controls, and this effect was greater in lower density cultures. Acute LIF treatment restricted to early time points increased the final number of bone nodules formed in mature RBM cell cultures, but not in RC cell cultures. Our results indicate that LIF exerts complex, stage-specific effects on osteoprogenitor recruitment, differentiation, and bone formation, and that the effects are cell nonautonomous, in the rat bone marrow stromal cell model. J. Cell. Biochem. Suppl. 36: 63-70, 2001.
- Published
- 2001
44. Selective attachment of osteoprogenitors to laminin11Part of this work was previously presented in abstract form (J Bone Miner Res 11:S392; 1996 and J Bone Miner Res 12:S243; 1997)
- Author
-
Harvey A. Goldberg, Pierre D. Delmas, Luc Malaval, and Patricia Roche
- Subjects
Bone sialoprotein ,education.field_of_study ,Histology ,biology ,Physiology ,Endocrinology, Diabetes and Metabolism ,Population ,Tenascin ,Osteoblast ,Molecular biology ,Extracellular matrix ,Fibronectin ,medicine.anatomical_structure ,Cell culture ,Laminin ,Immunology ,biology.protein ,medicine ,education - Abstract
During endochondral ossification and bone remodeling, osteoprogenitors (OP) attach to the matrix and differentiate into osteoblasts. To identify matrix proteins binding specifically these precursors, fetal rat calvaria (RC) cells were plated for 5–20 min in serum-free medium, on wells coated with various proteins and saturated with bovine serum albumin (BSA) to block nonspecific binding sites. Adherent cells were either counted or grown to assess bone colony (nodule) formation. As each nodule originates from the clonal division of one OP, the ratio (nodules/100 cells attached) measures the proportion of OP among adherent cells. Of numerous purified matrix proteins tested, laminin-1 and tenascin inhibited cell attachment, whereas fibronectin, bone sialoprotein, and type I collagen increased cell attachment and others had no effect. Only laminin-1 and, to a lesser extent, tenascin, enriched the cell population in OP. Laminin-1 acted time- and dose-dependently. In experiments in which cell attachment to laminin-coated but unsaturated wells was ensured by plating for 24 h in 10% fetal calf serum, laminin-1 had no effect on cell attachment nor on OP differentiation. In contrast, repeated plating of RC cells on laminin-1-coated/saturated wells depleted the population in OP, confirming that OP selection was a cell-attachment effect. When RC cell populations isolated by successive collagenase extractions were compared, the highest rate of OP enrichment on laminin-1 was obtained with the earliest populations, which were the most responsive to dexamethasone, a marker of early OP stages. In conclusion, laminin-1 recruits in vitro, through a cell-attachment effect, OP present in early RC cell populations, of which laminins are abundant extracellular matrix components.
- Published
- 1999
45. LIF, but Not IL-6, Regulates Osteoprogenitor Differentiation in Rat Calvaria Cell Cultures: Modulation by Dexamethasone
- Author
-
Ashwani K. Gupta, Pierre D. Delmas, Jane E. Aubin, Fina Liu, and Luc Malaval
- Subjects
endocrine system ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Cellular differentiation ,Down-Regulation ,Endogeny ,Biology ,Leukemia Inhibitory Factor ,Polymerase Chain Reaction ,Dexamethasone ,Antigens, CD ,Osteogenesis ,Internal medicine ,Cytokine Receptor gp130 ,medicine ,Animals ,Orthopedics and Sports Medicine ,RNA, Messenger ,Autocrine signalling ,Receptor ,Glucocorticoids ,Cells, Cultured ,reproductive and urinary physiology ,Lymphokines ,Membrane Glycoproteins ,Interleukin-6 ,Stem Cells ,Skull ,Cell Differentiation ,Glycoprotein 130 ,Receptors, Interleukin-6 ,Growth Inhibitors ,biological factors ,Rats ,Cell biology ,Cytokine ,Endocrinology ,Cell culture ,embryonic structures ,Leukemia inhibitory factor ,hormones, hormone substitutes, and hormone antagonists ,Signal Transduction - Abstract
Cytokines of the interleukin 6 (IL-6) subfamily are a group of factors produced by osteoblasts and acting through the same transducing element, membrane protein gp130. We have previously shown that exogenous (added to the culture medium) leukemia inhibitory factor (LIF) inhibits bone nodule formation and expression of osteoblast-associated genes in fetal rat calvaria (RC) cell cultures and that dexamethasone (Dex) increases the ID50 of LIF. To investigate the respective roles of IL-6-related cytokines and receptors in osteprogenitor differentiation, and their regulatory interplay with Dex, we used reverse transcribed polymerase chain reaction, bioassay, and blocking antibody techniques to assess the time courses of LIF, IL-6, LIF transmembrane receptor, IL-6 receptor, and gp130 expression in RC cell cultures grown with and without Dex. The levels of the mRNAs for IL-6, LIF, and gp130 decreased concomitantly with the formation of bone nodules. Dex treatment, which stimulates bone nodule formation, reduced the expression of LIF and IL-6 mRNAs and IL-6 bioactivity in the culture medium. LIF treatment strongly stimulated the expression of IL-6. Incubation with anti-LIF antibodies increased the number of nodules, while an antibody blocking IL-6 activity had little or no effect on nodule numbers and did not antagonize the action of exogenous LIF, indicating that IL-6 does not mediate the action of LIF in this system. Moreover, although exogenously added IL-6 was active in the cultures as noted by a reduction of nodule mineralization, it had no effect on nodule numbers, i.e., on osteoprogenitor differentiation, in the presence or absence of Dex. In conclusion, IL-6, LIF, and their receptors are expressed throughout the time-course of osteogenesis in RC cell cultures. However, only LIF, but not IL-6, appears to play a significant role in autocrine regulation of osteoblastic differentiation in this system. The antagonist action of Dex on the effects of exogenously added LIF, as well as the bone-promoting action of Dex in RC cell cultures, could be exerted partly through the down-regulation of the expression of endogenous LIF.
- Published
- 1998
46. Spatiotemporal distribution of SPARC/Osteonectin in Developing and Mature Chicken Retina
- Author
-
Vitauts I. Kalnins, Sabrina Y. Kim, Nishita Ondhia, Maurice J. Ringuette, Luc Malaval, and Danka Vidgen
- Subjects
Pathology ,medicine.medical_specialty ,Molecular Sequence Data ,Outer plexiform layer ,Chick Embryo ,Retina ,Cellular and Molecular Neuroscience ,Morphogenesis ,medicine ,Animals ,Osteonectin ,Amino Acid Sequence ,RNA, Messenger ,Pigment Epithelium of Eye ,Outer nuclear layer ,Ganglion cell layer ,Conserved Sequence ,In Situ Hybridization ,Retinal pigment epithelium ,biology ,Blotting, Northern ,Inner plexiform layer ,Immunohistochemistry ,Sensory Systems ,Cell biology ,Ophthalmology ,medicine.anatomical_structure ,Microscopy, Fluorescence ,Inner nuclear layer ,biology.protein ,sense organs ,Chickens - Abstract
Expression of SPARC (Secreted Protein, Acidic, Rich in Cysteine), a counteradhesive, calcium-binding extracellular matrix (ECM) glycoprotein, is associated with several morphogenetic events during early development. In this study, changes in the spatiotemporal distribution of SPARC transcripts and the protein during chicken retinal development were documented by in situ hybridization and indirect immunofluorescence microscopy. SPARC transcripts were first detected within the proliferating neural ectoderm at embryonic day 4.5 (E4.5), followed short thereafter (E5) by appearance of SPARC. SPARC was enriched within the inner plexiform layer (IPL) by E10 and within the outer plexiform layer (OPL) by E14, several days after these layers became morphologically distinct. Significant levels of SPARC transcripts were first observed within the ganglion cell layer (GCL) at E17 prior to accumulation of SPARC within the nerve fiber layer, seen first at E20. SPARC protein was first detected within the developing retinal pigment epithelium (RPE) at E10 and increased significantly at RPE cells ceased to proliferate and continued differentiating. Of special note was the restriction of SPARC to the basal-half of the RPE cells. SPARC transcripts were similarly distributed in the adult retina, but at lower levels than in the period just prior to hatching. In the adult retina SPARC was retained in the nerve fiber layer and present in the inner nuclear layer (INL) and outer nuclear layer (ONL), but lost from the IPL and OPL. These changes in expression pattern with time indicate that SPARC is developmentally regulated and therefore may have important function(s) in both morphological development of the retina and functioning of the mature eye.
- Published
- 1997
47. Decorin inhibits cell attachment to thrombospondin-1 by binding to a KKTR-dependent cell adhesive site present within the N-terminal domain of thrombospondin-1
- Author
-
Jack Lawler, Philippe Clézardin, Pierre D. Delmas, Blandine Merle, and Luc Malaval
- Subjects
endocrine system ,Decorin ,Recombinant Fusion Proteins ,Molecular Sequence Data ,Plasma protein binding ,Biochemistry ,Bone and Bones ,3T3 cells ,Cell Line ,Thrombospondin 1 ,Mice ,chemistry.chemical_compound ,Cell Adhesion ,otorhinolaryngologic diseases ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Binding site ,Cell adhesion ,Molecular Biology ,Peptide sequence ,Skin ,Extracellular Matrix Proteins ,Osteoblasts ,biology ,virus diseases ,3T3 Cells ,Cell Biology ,Heparan sulfate ,Cell biology ,medicine.anatomical_structure ,chemistry ,Proteoglycan ,biology.protein ,Cattle ,Proteoglycans ,Heparitin Sulfate ,Peptides ,Protein Binding - Abstract
Skin decorin (DCN) is an antiadhesive dermatan sulfate-rich proteoglycan that interacts with thrombospondin-1 (TSP) and inhibits fibroblast adhesion to TSP [Winnemöller et al., 1992]. Molecular mechanisms by which DCN interacts with TSP and inhibits cell adhesion to TSP are unknown. In the present study, we showed that skin DCN and bone DCN (chondroitin sulfate-rich proteoglycan) were quantitatively identical with respect to their ability to interact with TSP. Using a series of fusion proteins corresponding to the different structural domains of TSP, binding of [125I]DCN to TSP was found to be dependent of the N-terminal domain and, to a lesser extent, of the type 1 repeats and the C-terminal domain of TSP. In addition, heparan sulfate drastically inhibited [125I]DCN binding to solid-phase adsorbed TSP (80% inhibition), suggesting that DCN could bind to the N-terminal domain of TSP through interaction with heparin-binding sequences. To address this question, a series of synthetic peptides, overlapping heparin-binding sequences ARKGSGRR (residues 22-29), KKTR (residues 80-83) and RLRIAKGGVNDN (residues 178-189), were synthesized and tested for their ability to interact with DCN. [125I]DCN interacted only with peptides VDAVRTEKGFLLLASLRQMKKTRGT and KKTRGTLLALERKDHS containing the heparin-binding consensus sequence KKTR. These peptides contained glycosaminoglycan-dependent and -independent binding sites because [125I]DCN binding to VDAVRTEKGFLLLASLRQMKKTRGT and KKTRGTLLALERKDHS was partially reduced upon removal of the glycosaminoglycan chain (65% and 46% inhibition, respectively). [125I]DCN poorly bound to subpeptide MKKTRG and did not bind at all to subpeptides VDAVRTEKGFLLLASLRQ and TLLALERKDHS, suggesting that heparin-binding sequence MKKTRG constituted a DCN binding site when flanked with peptides VDAVRTEKGFLLLASLRQ and TLLALERKDHS. The sequence VDAVRTEKGFLLLASLRQMKKTRGTLLALERKDHS constitutes a cell adhesive active site in the N-terminal domain of TSP [Clezardin et al., 1997], and DCN inhibited the attachment of fibroblastic and osteoblastic cells to peptides VDAVRTEKGFLLLASLRQMKKTRGT and KKTRGTLLALERKDHS by about 50 and 80%, respectively. Although fibroblastic cells also attached to type 3 repeats and the C-terminal domain of TSP, DCN only inhibited cell attachment to the C-terminal domain. Overall, these data indicate that modulation by steric exclusion of cell adhesion to a KKTR-dependent cell adhesive site present within the N-terminal domain of TSP could explain the antiadhesive properties of DCN.
- Published
- 1997
48. The Mature Osteoblast Phenotype Is Characterized by Extensive Plasticity
- Author
-
Fina Liu, Jane E. Aubin, and Luc Malaval
- Subjects
Bone sialoprotein ,medicine.medical_specialty ,Cell type ,Sialoglycoproteins ,Molecular Sequence Data ,Osteocalcin ,Immunocytochemistry ,Internal medicine ,medicine ,Animals ,Integrin-Binding Sialoprotein ,Amino Acid Sequence ,Osteopontin ,Rats, Wistar ,Cuboidal Cell ,Osteoblasts ,biology ,Osteoid ,Stem Cells ,Skull ,Osteoblast ,Cell Biology ,Alkaline Phosphatase ,Antigens, Differentiation ,Immunohistochemistry ,Clone Cells ,Rats ,Cell biology ,Phenotype ,Endocrinology ,medicine.anatomical_structure ,biology.protein ,Collagen - Abstract
While both morphological and biochemical-molecular attributes demarcate differentiation stages in specific cell and tissue types, what constitutes necessary and sufficient expression to define particular cell types is not always known. For example, mature osteoblasts (OBs) are defined morphologically as the cuboidal, biosynthetically active, basophilic cells residing on bone surfaces and responsible for the deposition of osteoid matrix. However, several recent observations suggest that not all mature OBs are identical. To explore further the validity of the hypothesis that heterogeneity of phenotype exists among mature OBs, we grew fetal rat calvaria cells in vitro at low density under conditions in which bone nodules form and mineralize in isolation of other contaminating cell and colony types. Cells resident in mature OB colonies, i.e., those comprising mainly cuboidal cells associated with an osteoid matrix that had begun to mineralize, were analyzed in situ for protein expression by immunocytochemistry with antibodies against collagen type I, alkaline phosphatase, osteopontin, bone sialoprotein, and osteocalcin. Consistent with the expected phenotype of mature OBs, many OBs expressed high levels of all of these markers, but strikingly even adjacent morphologically indistinguishable cuboidal OBs had differences in protein expression, especially in relation to osteopontin, bone sialoprotein, and osteocalcin expression. Double-labeling with Hoechst 33258 and osteocalcin indicated that the variation in antibody labeling intensity/protein expression appeared independent of a variation in cell cycle. To further ascertain the extent of this heterogeneity, 20 single cells were micromanipulated from colonies and subjected to poly(A)-PCR to analyze the simultaneous coexpression profiles of the same five markers analyzed by immunocytochemistry and two other markers, the OB-osteocyte transition marker E11 and the parathyroid hormone/parathyroid hormone-related protein receptor. Notably, the repertoire of genes expressed and their levels of expression varied markedly in individual OBs. The observed heterogeneity suggests that the mature OB phenotype is not a single unique phenotype but rather encompasses a flexible pattern of expression from the repertoire of OB-associated markers.
- Published
- 1997
49. Parathyroid hormone 1-84 targets bone vascular structure and perfusion in mice: impacts of its administration regimen and of ovariectomy
- Author
-
Bernard, Roche, Arnaud, Vanden-Bossche, Luc, Malaval, Myriam, Normand, Martin, Jannot, Robin, Chaux, Laurence, Vico, and Marie-Hélène, Lafage-Proust
- Subjects
Time Factors ,Diphosphonates ,Tibia ,Ovariectomy ,Hemodynamics ,Imidazoles ,X-Ray Microtomography ,Propranolol ,Zoledronic Acid ,Mice, Inbred C57BL ,Perfusion ,Osteogenesis ,Parathyroid Hormone ,Animals ,Female - Abstract
Bone vessel functions during bone remodeling are poorly understood. They depend on both vessel network structure and vasomotor regulation. Parathyroid hormone (PTH) is a systemic vasodilator that may modulate microvascularization. Moreover, although intermittent PTH is anti-osteoporotic, continuous PTH administration can be catabolic for bone. Finally, ovariectomy (OVX) reduces bone perfusion and vessel density in mice. We reasoned that the effects of PTH on bone vascularization might depend on its administration regimen and be impacted by ovariectomy. A 100-µg/kg PTH 1-84 daily dose was administered for 15 days to 4-month-old female C57BL/6 mice, either as daily sc injection (iPTH) or continuously (cPTH; ALZET minipump). Blood pressure (BP) and tibia bone perfusion were measured in vivo with a laser Doppler device. Histomorphometry of bone and barium-contrasted vascular network were performed on the same tibia. Compared with untreated controls, both iPTH and cPTH increased bone formation but had opposite effects on resorption. Both iPTH and cPTH were slightly angiogenic. Intermittent PTH increased microvessel size (+48%, p0.001), whereas cPTH decreased it (-29%, p = 0.009). iPTH increased bone perfusion (27%, p0.001) with no change in BP, whereas cPTH did not. The vascular effects of a 15-day iPTH treatment were analyzed in OVX mice and compared with sham-operated and OVX untreated controls. Two other anti-osteoporotic drugs, zoledronate (one injection, 70 µg/kg) and propranolol, (5 mg/kg/d) were tested in OVX mice. Although no change in bone mass was observed, iPTH stimulated bone formation and prevented the OVX-induced reduction in bone perfusion and vessel density. Both zoledronate and propranolol strongly lowered bone turnover, but surprisingly, zoledronate prevented OVX-induced reduction in bone perfusion but propranolol did not. Our integrative approach thus demonstrates that the effects of PTH on bone vessel structure and function depend on its mode of administration as well as on the HPG-axis hormonal status, and that OVX-induced vascular changes are prevented by iPTH.
- Published
- 2013
50. Validated Laser Doppler protocol for measurement of mouse bone blood perfusion - response to age or ovariectomy differs with genetic background
- Author
-
Myriam Normand, Luc Malaval, Laurence Vico, Bernard Roche, Marie-Hélène Lafage-Proust, Arnaud Vanden-Bossche, Tissu Osseux et Contraintes Mecaniques (LBTO), Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Camille Jordan [Villeurbanne] (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Aging ,Histology ,Mice, 129 Strain ,Physiology ,Endocrinology, Diabetes and Metabolism ,Ovariectomy ,030209 endocrinology & metabolism ,Bone remodeling ,03 medical and health sciences ,Mice ,0302 clinical medicine ,In vivo ,Laser-Doppler Flowmetry ,Medicine ,Animals ,Tibia ,Pathological ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,0303 health sciences ,[STAT.AP]Statistics [stat]/Applications [stat.AP] ,business.industry ,Blood flow ,Laser Doppler velocimetry ,Adaptation, Physiological ,Mice, Inbred C57BL ,Radiography ,Osteoporosis ,Female ,business ,Perfusion ,Ex vivo - Abstract
The physiological role of bone vascularization in bone metabolism begins to be understood; however, its involvement in pathological situations remains poorly explored. Bone blood supply depends on both vascular density and blood flow. However, in mice, the specific evaluation of perfusion in bone suffers from a lack of easy-handling measurement tools. In the present study, we first developed a Laser Doppler Perfusion Measurement (LDPM) protocol in mouse tibia, which we validated with ex vivo and in vivo experiments. Then we carried out a study associating both structural (vascular quantitative histomorphometry) and functional (LDPM) approaches. We studied the effects of aging in 4, 7 and 17 month-old male mice and the early effects of ovariectomy in 4 month-old females. Both studies were carried out in inbred mice (C57BL/6) and in mice of mixed background (129sv/CD1). The significant differences we observed between strains in unchallenged 4 month-old animals concerned both perfusion and vascular density and depended on gender. Additionally, the age-related bone loss observed in male mice was not temporally associated with vascular changes in either strain. Between 7 and 17 months, we did not find any decrease in bone vascular density or perfusion. In contrast, ovariectomy triggered early vascular structural and functional adaptations which differed between genetic backgrounds. We observed that bone vessel density did not generally account for bone perfusion levels. In conclusion, we describe here a LDPM-based experimental protocol which provides a reproducible quantitative evaluation of bone perfusion in mouse tibia, hence allowing intergroup comparisons. This integrative structural and functional approach of bone vascularization showed that bone vascular adaptation occurs during aging or after ovariectomy and is affected by the genetic background.
- Published
- 2013
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