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1. Inhibition of alkaline phosphatase impairs dyslipidemia and protects mice from atherosclerosis

Author

Laurence Bessueille, Lynn Kawtharany, Thibaut Quillard, Claudia Goettsch, Anne Briolay, Nirina Taraconat, Stéphane Balayssac, Véronique Gilard, Saida Mebarek, Olivier Peyruchaud, François Duboeuf, Caroline Bouillot, Anthony Pinkerton, Laura Mechtouff, René Buchet, Eva Hamade, Kazem Zibara, Caroline Fonta, Emmanuelle Canet-soulas, Jose luis Millan, David Magne, Fonta, Caroline, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Interactions moléculaires et réactivité chimique et photochimique (IMRCP), Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-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 Grenoble Alpes (UGA), Sanford Burnham Prebys Medical Discovery Institute, Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Lebanese University [Beirut] (LU), Centre de recherche cerveau et cognition (CERCO UMR5549), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Fluides, Energie, Réacteurs, Matériaux et Transferts (FERMAT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), BIBAC - Chimie analytique et interactions biomolécules - matière molle biomimétique (BIBAC), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-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 Grenoble Alpes (UGA), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)

Subjects
calcification, inflammation, Physiology (medical), Biochemistry (medical), Public Health, Environmental and Occupational Health, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, General Medicine, TNAP, liver, metabolic syndrome
Abstract

International audience; Calcium accumulation in atherosclerotic plaques predicts cardiovascular mortality, but the mechanisms responsible for plaque calcification and how calcification impacts plaque stability remain debated. Tissue-nonspecific alkaline phosphatase (TNAP) recently emerged as a promising therapeutic target to block cardiovascular calcification. In this study, we sought to investigate the effect of the recently developed TNAP inhibitor SBI-425 on atherosclerosis plaque calcification and progression. TNAP levels were investigated in ApoE-deficient mice fed a high-fat diet from 10 weeks of age and in plaques from the human ECLAGEN biocollection (101 calcified and 14 non-calcified carotid plaques). TNAP was inhibited in mice using SBI-425 administered from 10 to 25 weeks of age, and in human vascular smooth muscle cells (VSMCs) with MLS-0038949. Plaque calcification was imaged in vivo with 18F-NaF-PET/CT, ex vivo with osteosense, and in vitro with alizarin red. Bone architecture was determined with µCT. TNAP activation preceded and predicted calcification in human and mouse plaques, and TNAP inhibition prevented calcification in human VSMCs and in ApoE-deficient mice. More unexpectedly, TNAP inhibition reduced the blood levels of cholesterol and triglycerides, and protected mice from atherosclerosis, without impacting the skeletal architecture. Metabolomics analysis of liver extracts identified phosphocholine as a substrate of liver TNAP, who's decreased dephosphorylation upon TNAP inhibition likely reduced the release of cholesterol and triglycerides into the blood. Systemic inhibition of TNAP protects from atherosclerosis, by ameliorating dyslipidemia, and preventing plaque calcification.

Published
2022
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2. Influence of Loading Conditions in Finite Element Analysis Assessed by HR-pQCT on Ex Vivo Fracture Prediction

Author

David Mitton, Hélène Follet, Martin Revel, François Duboeuf, François Bermond, Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biomécanique et Mécanique des Chocs (LBMC UMR T9406 ), Université de Lyon-Université de Lyon-Université Gustave Eiffel, and Cadic, Ifsttar

Subjects
musculoskeletal diseases, Histology, Materials science, Physiology, Endocrinology, Diabetes and Metabolism, Finite Element Analysis, FORWARD FALL, 030209 endocrinology & metabolism, 03 medical and health sciences, 0302 clinical medicine, Absorptiometry, Photon, Bone Density, medicine, FRACTURE PREDICTION, Humans, Tibia, Quantitative computed tomography, 030304 developmental biology, Bone mineral, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Receiver operating characteristic, medicine.diagnostic_test, RADIUS, Torsion (mechanics), Radius, musculoskeletal system, Finite element method, HR-PQCT, Fracture (geology), Osteoporotic Fractures, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Biomedical engineering, BONE STRENGTH
Abstract

Many fractures occur in individuals with normal areal Bone Mineral Density (aBMD) measured by Dual X-ray Absorptiometry (DXA). High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) allows for non-invasive evaluation of bone stiffness and strength through micro finite element (?FE) analysis at the tibia and radius. These ?FE outcomes are strongly associated with fragility fractures but do not provide clear enhancement compared with DXA measurements. The objective of this study was to establish whether a change in loading conditions in standard ?FE analysis assessed by HR-pQCT enhance the discrimination of low-trauma fractured radii (n = 11) from non-fractured radii (n = 16) obtained experimentally throughout a mechanical test reproducing a forward fall. Micro finite element models were created using HR-pQCT images, and linear analyses were performed using four different types of loading conditions (axial, non-axial with two orientations and torsion). No significant differences were found between the failure load assessed with the axial and non-axial models. The different loading conditions tested presented the same area under the receiver operating characteristic (ROC) curves of 0.79 when classifying radius fractures with an accuracy of 81.5%. In comparison, the area under the curve (AUC) is 0.77 from DXA-derived ultra-distal aBMD of the forearm with an accuracy of 85.2%. These results suggest that the restricted HR-pQCT scanned region seems not sensitive to loading conditions for the prediction of radius fracture risk based on ex vivo experiments (n = 27).

Published
2021
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3. Dual-energy CT hybridation and kernel processing effects on the estimation of bone mineral mass and density: a calcination study on ex vivo human femur

Author

Jean-Paul Roux, François Bermond, Philippe Paul Wagner, Jean-Baptiste Pialat, Pawel Szulc, Quentin Chuzel, François Duboeuf, Roland Chapurlat, Hélène Follet, Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Laboratoire de Biomécanique et Mécanique des Chocs (LBMC UMR T9406 ), and Université de Lyon-Université de Lyon-Université Gustave Eiffel

Subjects
CALCINATION, DUAL-ENERGY CT, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Absorptiometry, Photon, 0302 clinical medicine, Bone Density, Humans, Medicine, Femur, Quantitative computed tomography, Bone mineral, DXA, Minerals, medicine.diagnostic_test, Femur Neck, business.industry, KERNELS, SPECTRAL IMAGING, Human femur, Image contrast, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Kernel (statistics), Reference values, Bone mineral content, Dual energy ct, Tomography, X-Ray Computed, business, Biomedical engineering
Abstract

INTRODUCTION Recent technological advances with dual-energy quantitative computed tomography (DEQCT) allow to combine two images of different level of energy to obtain simulated mono-energetic images at 60 keV (SIM60KeV-QCT) with improved image contrast in clinical practice. This study includes three topics: (1) compare bone mineral content (BMC), areal and volumetric bone mineral density (aBMD, vBMD) obtained with SIM60KeV-QCT, single-energy QCT (SEQCT), and dual X-ray absorptiometry (DXA); (2) compare ash density and weight with respective vBMD and BMC assessed on SIM60KeV-QCT, SEQCT, and DXA; and (3) compare the influence of reconstruction kernels on the accuracy of vBMD and BMC using ash density and ash weight as the reference values. METHODS DXA, SEQCT, and DEQCT acquisitions were performed ex vivo on 42 human femurs. Standard kernel (SK) and bone kernel (BK) were applied to each stack of images. Ten diaphyses and 10 femoral necks were cut, scanned, and reconstructed using the techniques described above. Finally, the bone specimens were calcined to obtain the ash weight. RESULTS QCT analysis (SEQCT, SIM60KeV-QCT) underestimated BMC value compared to DXA. For femoral necks, all QCT analyses provided an unbiased estimate of ash weight but underestimated ash density regardless of the kernel used. For femoral diaphysis, SEQCT BK, SIM60KeV-QCT BK, and SK underestimated ash weight but not ash density. CONCLUSION BMC and vBMD quantifications with the SIM60KeV-QCT gave similar results as the SEQCT. Further studies are needed to optimize the use of SIM60KeV-QCT in clinical situations. SK should be used given the effect of kernels on QCT assessment.

Published
2021
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4. DXA body composition corrective factors between Hologic Discovery models to conduct multicenter studies

Author

Bernard Cortet, Eric Lespessailles, François Duboeuf, Roland Chapurlat, Jean-Paul Roux, Thibault Sutter, Imagerie Multimodale Multiéchelle et Modélisation du Tissu Osseux et articulaire (I3MTO), Université d'Orléans (UO), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Marrow Adiposity & Bone Lab - Adiposité Médullaire et Os - ULR 4490 (MABLab (ex-pmoi)), Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and CCSD, Accord Elsevier

Subjects
0301 basic medicine, Histology, Physiology, Endocrinology, Diabetes and Metabolism, Coefficient of variation, 030209 endocrinology & metabolism, Bone and Bones, Imaging phantom, Fat mass, 03 medical and health sciences, Absorptiometry, Photon, 0302 clinical medicine, Bone Density, Humans, Medicine, Densitometer, ComputingMilieux_MISCELLANEOUS, Bone mineral, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Phantoms, Imaging, business.industry, Cross Calibration, 030104 developmental biology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Body Composition, Lean body mass, Bone mineral content, business, Nuclear medicine
Abstract

Background Dual X-ray absorptiometry body composition measurements are widely used for clinical and research settings. It is well known that measurements vary across instruments, needing caution for longitudinal monitoring or multicentric studies. This study was to quantify intra- and inter-center variability of bone mineral content, bone mineral density, fat and lean body composition measurements between Hologic Discovery models in order to calculate the corrective factors to be applied for multicenter research projects. Materials and methods A whole body phantom composed of materials representing the thickness and percentage of bone, lean and fat mass in the human physiological range was analyzed ten times in three different centers using dual energy X-ray absorptiometry scanners (Two Hologic Discovery QDR A and one QDR W). In addition, we used a morphometric vertebral phantom to monitor stability and a three steps block phantom to check accuracy. Results We found a good long-term stability and accuracy for the three devices. Intra-center coefficients of variation were within the range of the manufacturer acceptable values (bone mineral density: 1.40%, bone mineral content: 1%, area: 1.50%, fat mass: 0.89%, lean mass: 0.76%, total mass: 0.12%). Whereas the inter-center coefficient of variation exceeded 8% (bone mineral density: 8.18%, bone mineral content: 3.03%, area: 8.63%: fat mass: 3,92%, lean mass: 7.89%, total mass: 2.85%). Conclusion Our study showed that the discrepancies across centers remain a major concern, particularly with regard to body composition results. Our study highlight the need of cross calibration between densitometers and proposes corrective factors evaluated from a whole body phantom to lead multicentric studies adjustment.

Published
2021
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5. Expression of the type 1 lysophosphatidic acid receptor in osteoblastic cell lineage controls both bone mineralization and osteocyte specification

Author

Irma Machuca-Gayet, Hélène Follet, Jean-Pierre Salles, Jerold Chun, Isabelle Gennero, Sara Laurencin-Dalacieux, Daniel Bouvard, François Duboeuf, Amri Saber, Richard Rivera, Nicolas Beton, Candide A. Alioli, Delphine Farlay, Léa Demesmay, Olivier Peyruchaud, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Sanford Burnham Prebys Medical Discovery Institute, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), This work was supported by grants from the Institut National de la Santé Et de la Recherche Médicale, the Université Claude Bernard Lyon 1, the Agence Nationale de la Recherche (Grant LYSBONE No. ANR-15-CE14-0010), the Région d’Occitanie (grant Rbio N°15065647), Ipsen Pharma France, Lilly France and Pfizer France., ANR-15-CE14-0010,LYSBONE,Acide lysophosphatidique et contrôle de la masse osseuse(2015), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Peyruchaud, Olivier, and Acide lysophosphatidique et contrôle de la masse osseuse - - LYSBONE2015 - ANR-15-CE14-0010 - AAPG2015 - VALID

Subjects
0301 basic medicine, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Lpar1, Cellular differentiation, 030209 endocrinology & metabolism, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Osteocytes, Bone remodeling, Mice, 03 medical and health sciences, 0302 clinical medicine, Bone Density, Osteogenesis, Bone cell, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, Animals, Receptors, Lysophosphatidic Acid, Bone, Molecular Biology, Mice, Knockout, Bone growth, Mice, Inbred BALB C, LPA(1), Osteoblasts, LPAR1, [SDV.OT] Life Sciences [q-bio]/Other [q-bio.OT], Chemistry, Osteoblast, Osteocyte, Cell Biology, DMP1, Cell biology, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, Knockout mice
Abstract

International audience; Lysphosphatidic acid (LPA) is a major natural bioactive lipid mediator whose biological functions affect multiple organs. These include bone as demonstrated by global Lpar1-knockout mice (Lpar1-/-) which present a bone growth defect. LPA acts on all bone cells including osteoblasts, that are responsible for bone formation, and osteoclasts, which are specialized cells that resorb bone. LPA appears as a potential new coupling molecule during bone remodeling. LPA1 is the most ubiquitous LPA receptor among the six LPA receptor family members (LPA1-6). To better understand the specific role of LPA via its receptor LPA1 in osteoblastic cell lineage we generated osteoblast-specific Lpar1 knockout mice (Lpar1-∆Ob) by crossing Lpar1flox/flox and Osx:Cre+ mouse lines. Lpar1-∆Ob mice do not recapitulate the bone defects of Lpar1-/- mice but revealed reduced bone mineralization and decreased cortical thickness, as well as increased bone porosity associated with an augmentation in the lacunae areas of osteocyte and their apoptotic yield. In vitro, primary Lpar1-∆Ob and immortalized cl1-Ob-Lpar1-/- osteoblasts revealed a remarkable premature expression of alkaline phosphatase, reduced cell proliferation associated with decreased YAP-P nuclear accumulation, and reduced mineralization activity. Osteocyte specification is markedly impaired as demonstrated by reduced expression of early (E11) and late (DMP1, DKK1, SOST) osteocyte markers ex vivo in enriched osteocytic fractions of Lpar1-∆Ob mouse bone explants. In addition, E11 expression and dendrite formation induced by FGF2 are markedly impaired in both primary Lpar1-∆Ob and immortalized cl1-Ob-Lpar1-/- osteoblasts. Taken together these results suggest a new role for LPA in bone mass control via bone mineralization and osteocyte function.

Published
2020
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6. Osteoclast‐Derived Autotaxin, a Distinguishing Factor for Inflammatory Bone Loss

Author

Fabienne Coury, Fanny Bourguillault, Gabor Tigyi, Jean-Luc Davignon, Derek D. Norman, François Duboeuf, Sacha Flammier, Irma Machuca-Gayet, Olivier Peyruchaud, Sylvie Isaac, Hubert Marotte, Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pierre-Paul Riquet [Toulouse], CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP - U1043 INSERM - UMR5282 CNRS - UT3), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The University of Tennessee Health Science Center [Memphis] (UTHSC), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), 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), Centre de Physiopathologie Toulouse Purpan (CPTP), Machuca-Gayet, Irma, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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
0301 basic medicine, Male, Necrosis, Arthritis, Osteoclasts, MESH: X-Ray Microtomography, Bone remodeling, Talus, Arthritis, Rheumatoid, Mice, 0302 clinical medicine, MESH: Arthritis, Rheumatoid / pathology, Immunology and Allergy, MESH: Animals, Femur, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, MESH: Talus / diagnostic imaging, 3. Good health, medicine.anatomical_structure, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, MESH: Tumor Necrosis Factor-alpha / genetics, 030220 oncology & carcinogenesis, Rheumatoid arthritis, Gene Knockdown Techniques, Tumor necrosis factor alpha, Female, medicine.symptom, Autotaxin, medicine.medical_specialty, Ovariectomy, Immunology, MESH: Ovariectomy, Inflammation, Mice, Transgenic, Article, 03 medical and health sciences, MESH: Bone Resorption / metabolism, Rheumatology, Osteoclast, Internal medicine, medicine, Animals, Humans, Bone Resorption, MESH: Mice, MESH: Osteoclasts / metabolism, MESH: Femur / diagnostic imaging, MESH: Humans, business.industry, Phosphoric Diester Hydrolases, Tumor Necrosis Factor-alpha, MESH: Bone Resorption / immunology, X-Ray Microtomography, medicine.disease, MESH: Gene Knockdown Techniques, Arthritis, Experimental, MESH: Bone Resorption / diagnostic imaging, Calcaneus, 030104 developmental biology, Endocrinology, MESH: Arthritis, Experimental / pathology, business
Abstract

International audience; OBJECTIVE : The severity of rheumatoid arthritis (RA) correlates directly with bone erosions arising from osteoclast (OC) hyperactivity. Despite the fact that inflammation may be controlled in patients with RA, those in a state of sustained clinical remission or low disease activity may continue to accrue erosions, which supports the need for treatments that would be suitable for long-lasting inhibition of OC activity without altering the physiologic function of OCs in bone remodeling. Autotaxin (ATX) contributes to inflammation, but its role in bone erosion is unknown. METHODS : ATX was targeted by inhibitory treatment with pharmacologic drugs and also by conditional inactivation of the ATX gene Ennp2 in murine OCs (ΔATXC tsk ). Arthritic and erosive diseases were studied in human tumor necrosis factor-transgenic (hTNF+/- ) mice and mice with K/BxN serum transfer-induced arthritis. Systemic bone loss was also analyzed in mice with lipopolysaccharide (LPS)-induced inflammation and estrogen deprivation. Joint inflammation and bone erosion were assessed by histology and micro-computed tomography. The role of ATX in RA was also examined in OC differentiation and activity assays. RESULTS : OCs present at sites of inflammation overexpressed ATX. Pharmacologic inhibition of ATX in hTNF+/- mice, as compared to vehicle-treated controls, significantly mitigated focal bone erosion (36% decrease; P < 0.05) and systemic bone loss (43% decrease; P < 0.05), without affecting synovial inflammation. OC-derived ATX was revealed to be instrumental in OC bone resorptive activity and was up-regulated by the inflammation elicited in the presence of TNF or LPS. Specific loss of ATX in OCs from mice subjected to ovariectomy significantly protected against the systemic bone loss and erosion that had been induced with LPS and K/BxN serum treatments (30% reversal of systemic bone loss [P < 0.01]; 55% reversal of erosion [P < 0.001]), without conferring bone-protective properties. CONCLUSION : Our results identify ATX as a novel OC factor that specifically controls inflammation-induced bone erosions and systemic bone loss. Therefore, ATX inhibition offers a novel therapeutic approach for potentially preventing bone erosion in patients with RA.

Published
2019
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7. Clinical cone beam computed tomography compared to high-resolution peripheral computed tomography in the assessment of distal radius bone

Author

François Duboeuf, C. de Charry, Stephanie Boutroy, Roland Chapurlat, R. Ellouz, Jean-Baptiste Pialat, Hélène Follet, Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), 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)-École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Cone beam computed tomography, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], High resolution, 030209 endocrinology & metabolism, Computed tomography, Radius bone, 03 medical and health sciences, 0302 clinical medicine, Bone Density, Cadaver, medicine, Humans, Quantitative computed tomography, Image resolution, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Contouring, medicine.diagnostic_test, business.industry, 030206 dentistry, Cone-Beam Computed Tomography, Peripheral, Radius, medicine.anatomical_structure, Female, Tomography, X-Ray Computed, business, Nuclear medicine
Abstract

Clinical cone beam computed tomography (CBCT) was compared to high-resolution peripheral quantitative computed tomography (HR-pQCT) for the assessment of ex vivo radii. Strong correlations were found for geometry, volumetric density, and trabecular structure. Using CBCT, bone architecture assessment was feasible but compared to HR-pQCT, trabecular parameters were overestimated whereas cortical ones were underestimated. HR-pQCT is the most widely used technique to assess bone microarchitecture in vivo. Yet, this technology has been only applicable at peripheral sites, in only few research centers. Clinical CBCT is more widely available but quantitative assessment of the bone structure is usually not performed. We aimed to compare the assessment of bone structure with CBCT (NewTom 5G, QR, Verona, Italy) and HR-pQCT (XtremeCT, Scanco Medical AG, Bruttisellen, Switzerland). Twenty-four distal radius specimens were scanned with these two devices with a reconstructed voxel size of 75 μm for Newtom 5G and 82 μm for XtremeCT, respectively. A rescaling-registration scheme was used to define the common volume of interest. Cortical and trabecular compartments were separated using a semiautomated double contouring method. Density and microstructure were assessed with the HR-pQCT software on both modality images. Strong correlations were found for geometry parameters (r = 0.98–0.99), volumetric density (r = 0.91–0.99), and trabecular structure (r = 0.94–0.99), all p

Published
2016
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8. Structural and behavioural analysis of children's cortical bones

Author

Emmanuelle Lefevre, Hélène Follet, S. Rizzo, François Duboeuf, Cécile Baron, Martine Pithioux, Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), GeoRessources, Institut national des sciences de l'Univers (INSU - CNRS)-Centre de recherches sur la géologie des matières premières minérales et énergétiques (CREGU)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Laboratoire de Biomécanique et Mécanique des Chocs (LBMC UMR T9406), and Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)

Subjects
Bone density, Adolescent, business.industry, Behavioural analysis, Biomedical Engineering, Dentistry, Bioengineering, General Medicine, Bone and Bones, Computer Science Applications, Human-Computer Interaction, Mineral density, Bone Density, Hardness, Child, Preschool, Fracture (geology), Medicine, Humans, [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], business, Child
Abstract

Children's bones are interesting from both the mechanical and the clinical point of view because they frequently show typical bone fractures (greenstick), which is obviously a different fracture mo...

Published
2014
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9. Hyperpolarized 3He MR for Sensitive Imaging of Ventilation Function and Treatment Efficiency in Young Cystic Fibrosis Patients with Normal Lung Fonction

Author

Philippe Reix, Sophie Gaillard, Françoise Aubert, Karim Mosbah, Elise Bannier, Yannick Crémillieux, Yves Berthezène, François Duboeuf, Katarzyna Cieslar, Zahir Salhi, Instituto de Tecnologia Ceramica, Universitat Jaume I, Centre de Recherche et d'Application en Traitement de l'Image et du Signal (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)-École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Economie et de Sociologie Rurales Appliquées à l'Agriculture et aux Espaces Ruraux (CESAER), Institut National de la Recherche Agronomique (INRA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Hospices Civils de Lyon (HCL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique (CIC), Centre d'Investigation Clinique, Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Service de Pédiatrie, Pneumologie, Allergologie et Mucoviscidose, Hôpital Femme Mère Enfant, European Project: 36297,PHELINET, Bannier, Elise, Polarized HElium Lung Imaging NETwork - PHELINET - 36297 - OLD, Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Johannes Gutenberg - Universität Mainz (JGU)

Subjects
Male, Pathology, Pancreatic disease, imagerieₚoumons, Cystic Fibrosis, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, MESH: Respiratory Function Tests, MESH: Pulmonary Ventilation, Cystic fibrosis, Helium, 030218 nuclear medicine & medical imaging, MESH: Magnetic Resonance Imaging, MESH: Helium, 0302 clinical medicine, Isotopes, MESH: Airway Obstruction, imagerieₚulmonaire, MESH: Child, Stage (cooking), Young adult, Child, ComputingMilieux_MISCELLANEOUS, MESH: Treatment Outcome, MESH: Statistics, Nonparametric, MESH: Respiratory Therapy, Respiratory disease, MESH: Administration, Inhalation, Magnetic Resonance Imaging, 3. Good health, Respiratory Function Tests, MESH: Reproducibility of Results, reseau_international, Treatment Outcome, Breathing, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Female, categₘixte, Radiology, medicine.symptom, medicine.medical_specialty, Respiratory Therapy, MESH: Isotopes, MESH: Cystic Fibrosis, Adolescent, imagerieₘethodologie_RMN, Asymptomatic, Sensitivity and Specificity, Statistics, Nonparametric, 03 medical and health sciences, Administration, Inhalation, medicine, Humans, Radiology, Nuclear Medicine and imaging, MESH: Adolescent, [SDV.IB] Life Sciences [q-bio]/Bioengineering, MESH: Humans, business.industry, Reproducibility of Results, Normal lung function, medicine.disease, MESH: Male, MESH: Sensitivity and Specificity, Airway Obstruction, 030228 respiratory system, business, Pulmonary Ventilation, MESH: Female
Abstract

International audience; PURPOSE: To assess the sensitivity of hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging for the detection of peripheral airway obstruction in younger cystic fibrosis (CF) patients showing normal spirometric results (mean forced expiratory volume in 1 second [FEV(1)], 112% +/- 14.5 [standard deviation]) and to observe the immediate effects of a single chest physical therapy (CPT) session, thereby comparing two image quantification techniques. MATERIALS AND METHODS: Ten pediatric CF patients (age range, 8-16 years) with normal spirometric results were included in this study after approval from the local research ethics committee. Spirometry followed by proton and hyperpolarized (3)He three-dimensional lung imaging were performed with a 1.5-T MR unit before and after 20 minutes of CPT. The number of ventilation defects per image (VDI) and the ventilated lung fraction (VF), defined as the ratio of ventilated lung volume divided by total lung volume, were quantified. RESULTS: Ventilation defects were found in all patients (mean VDI, 5.1 +/- 1.9; mean global VF, 78.5% +/- 12.3; and mean peripheral VF, 75.5% +/- 17.1) despite normal spirometric results. After CPT, disparate changes in the distribution of ventilation defects were observed but the average VDI and VF did not change significantly (mean VDI, 5.1 +/- 1.1; mean global VF, 83.5% +/- 12.2; and mean peripheral VF, 80.3% +/- 12.2). There was no correlation between FEV(1) and VDI (rho = -0.041, P = .863) or global VF (rho = -0.196, P = .408) values but peripheral VF and VDI were correlated (rho = -0.563, P = .011). CONCLUSION: Although spirometric results indicate normal lung function, the mean VDI in patients (5.1) found in this study is well above the VDI in healthy subjects (1.6) reported in the literature. A single CPT session induces disparate changes in the distribution and extent of ventilation defects.

Published
2010
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10. Characterization of hepatocellular carcinoma and colorectal liver metastasis by means of perfusion MRI

Author

Jean-Yves Mabrut, François Duboeuf, Agnès Rode, Yves Berthezène, Christian Ducerf, Brigitte Bancel, Marlène Wiart, Siraj Saadaldin Abdullah, Jacques Baulieux, Jean-Baptiste Pialat, Laboratoire Creatis, Compte Général, Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Liver perfusion, Pathology, medicine.medical_specialty, Carcinoma, Hepatocellular, Contrast Media, Statistics, Nonparametric, 030218 nuclear medicine & medical imaging, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Meglumine, medicine, Carcinoma, Image Processing, Computer-Assisted, Organometallic Compounds, Humans, Radiology, Nuclear Medicine and imaging, business.industry, Significant difference, Liver Neoplasms, Cancer, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 3. Good health, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Female, Nuclear medicine, business, Colorectal Neoplasms, Perfusion, medicine.drug
Abstract

To characterize and compare hepatocellular carcinoma and liver metastases of colorectal metastatic cancer (CMC) by means of quantitative liver perfusion MRI.Liver perfusion was assessed in 26 HCC and CMC patients (50 nodules) by means of contrast-enhanced MRI. Six perfusion parameters-hepatic perfusion index (HPI), mean transit time (MTT), distribution volume (DV), total blood flow (F(T)), arterial blood flow (F(A)), and portal blood flow (F(P))-were calculated in tumor nodules and the adjacent hepatic parenchyma.The values of F(T), F(A), F(P), and DV were significantly higher in the HCC than in the CMC group, whereas MTT was significantly higher in the CMC group. There was no significant difference in HPI. Arterial blood flow was higher than portal blood flow in the CMC group, while portal blood flow was slightly higher than arterial blood flow in the HCC group.The present work describes the use of dynamic MRI to quantitatively assess liver perfusion, which in the future may help studying liver cancers on the basis of their microvascular characteristics.

Published
2008

11. Imagerie de la deformation des tissus biologiques par elastographie main-libre

Author

Olivier Basset, J.-F. Deprez, Elisabeth Brusseau, François Duboeuf, Centre de Recherche et d'Application en Traitement de l'Image et du Signal (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)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Laboratoire Creatis, Compte Général

Subjects
Pathology, medicine.medical_specialty, Materials science, [INFO.INFO-TS] Computer Science [cs]/Signal and Image Processing, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, [SPI.MECA.MEFL] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph], Image processing, Deformation (meteorology), Agar gel, [SPI.MECA.MEMA] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Mechanics of materials [physics.class-ph], [SPI.MECA.MEFL]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph], [PHYS.MECA.MEMA]Physics [physics]/Mechanics [physics]/Mechanics of materials [physics.class-ph], Elasticity Imaging Techniques, [PHYS.MECA.MEMA] Physics [physics]/Mechanics [physics]/Mechanics of materials [physics.class-ph], [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, [SPI.MECA.BIOM] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], [SPI.MECA.MEMA]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Mechanics of materials [physics.class-ph], medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, [PHYS.MECA.MEFL] Physics [physics]/Mechanics [physics]/Fluid mechanics [physics.class-ph], Radiology, Nuclear Medicine and imaging, [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing, [SDV.IB] Life Sciences [q-bio]/Bioengineering, [SPI.ACOU]Engineering Sciences [physics]/Acoustics [physics.class-ph], [SPI.ACOU] Engineering Sciences [physics]/Acoustics [physics.class-ph], Radiological and Ultrasound Technology, medicine.diagnostic_test, [PHYS.MECA.MEFL]Physics [physics]/Mechanics [physics]/Mechanics of the fluids [physics.class-ph], business.industry, Ultrasound, [PHYS.MECA.BIOM] Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], [PHYS.MECA.ACOU]Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph], [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Similarity criterion, [INFO.INFO-TI] Computer Science [cs]/Image Processing [eess.IV], [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], [SDV.IB]Life Sciences [q-bio]/Bioengineering, Elastography, Imaging technique, [PHYS.MECA.ACOU] Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph], business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Biomedical engineering
Abstract

An imaging technique of deformation under load of a biological soft tissue, from numerical processing of radiofrequency ultrasound images is presented. The 2D locally regularized estimation method determines deformation parameters as the arguments that maximize a similarity criterion between a pre-compression region and its deformed version, compensated for according to these parameters. The technique was assessed with ultrasound data acquired during freehand scanning on two dedicated elastography phantoms as well as ex vivo bovine liver samples, containing artificial lesions made with agar gel. Although the load conditions are complex, elastograms are easy to interpret, exhibiting the inclusions with sharp boundaries.

Published
2007

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