50 results on '"Bjorn R. Olsen"'
Search Results
2. Vascular endothelial growth factor control mechanisms in skeletal growth and repair
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Bjorn R. Olsen and Kai Hu
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0301 basic medicine ,Bone growth ,Angiogenesis ,Anatomy ,Bone healing ,Biology ,Cell biology ,Bone remodeling ,Vascular endothelial growth factor ,03 medical and health sciences ,Vascular endothelial growth factor A ,chemistry.chemical_compound ,030104 developmental biology ,chemistry ,Intramembranous ossification ,Endochondral ossification ,Developmental Biology - Abstract
Vascular endothelial growth factor A (VEGF) is a critical regulator of vascular development and postnatal angiogenesis and homeostasis, and it is essential for bone development and repair. Blood vessels serve both as structural templates for bone formation and they provide essential cells, growth factors and minerals needed for synthesis and mineralization, as well as turnover, of the extracellular matrix in bone. Through its regulation of angiogenesis, VEGF contributes to coupling of osteogenesis to angiogenesis, and it directly controls the differentiation and function of osteoblasts and osteoclasts. In this review, we summarize the properties of VEGF and its receptors that are relevant to bone formation and repair; the roles of VEGF during development of endochondral and membranous bones; and the contributions of VEGF to bone healing during different phases of bone repair. Finally, we discuss contributions of altered VEGF function in inherited disorders with bone defects as part of their phenotypes, and we speculate on what will be required before therapeutic strategies based on VEGF modulation can be developed for clinical use to treat patients with bone growth disorders and/or compromised bone repair. Developmental Dynamics 246:227-234, 2017. © 2016 Wiley Periodicals, Inc.
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- 2016
3. Soluble VEGFR1 reverses BMP2 inhibition of intramembranous ossification during healing of cortical bone defects
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Bjorn R. Olsen, Tatiana Y. Besschetnova, and Kai Hu
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0301 basic medicine ,Periosteum ,animal structures ,Chemistry ,Cartilage ,fungi ,Bone healing ,Bone morphogenetic protein 2 ,biological factors ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Osteoclast ,030220 oncology & carcinogenesis ,embryonic structures ,Intramembranous ossification ,medicine ,Orthopedics and Sports Medicine ,Cortical bone ,Endochondral ossification - Abstract
BMP2 is widely used for promotion of bone repair and regeneration. However, bone formation induced by BMP2 is quite variable. Bone forming progenitor cells in different locations appear to respond to BMP2 in different ways, and repair outcomes can vary as a consequence of modulating effects by other factors. In this study, we have examined the effects of VEGF on BMP2-induced repair of a cortical bone defect, a 1 mm diameter drill hole, in the proximal tibia of mice. Treatment of the defect with either a bolus of PBS or soluble VEGFR1 (sVEGFR1), a decoy receptor for VEGF, had the same effects on bone formation via intramembranous ossification in the defect and cartilage formation and injured periosteum, during the healing process. In contrast, treatment with BMP2 inhibited intramembranous bone formation in the defect while it promoted cartilage and endochondral bone formation in the injured periosteum compared with mice treated with PBS or sVEGFR1. The inhibitory effect of BMP2 on bone formation was unlikely due to increased osteoclast activity and decreased invasion of blood vessels in the defect. Most importantly, co-delivery of BMP2 and sVEGFR1 reversed the inhibition of intramembranous bone formation by BMP2. Furthermore, the decreased accumulation of collagen and production of bone matrix proteins in the defect of groups with BMP2 treatment could also be prevented by co-delivery of BMP2 and sVEGFR1. Our data indicate that introducing a VEGF-binding protein, such as sVEGFR1, to reduce levels of extracellular VEGF, may enhance the effects of BMP2 on intramembranous bone formation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1461-1469, 2017.
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- 2016
4. Fell-Muir Lecture: Regulatory mechanisms of skeletal and connective tissue development and homeostasis - lessons from studies of human disorders
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Tatiana Y. Besschetnova, Bjorn R. Olsen, Kai Hu, Agnes D. Berendsen, and Xuchen Duan
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Vascular Endothelial Growth Factor A ,0301 basic medicine ,medicine.medical_specialty ,Connective tissue ,Receptors, Cell Surface ,Biology ,Pathology and Forensic Medicine ,Hemangioma ,Extracellular matrix ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Fibrosis ,Internal medicine ,medicine ,Animals ,Homeostasis ,Humans ,Receptor ,Molecular Biology ,Bone Development ,Microfilament Proteins ,NFAT ,Cell Biology ,medicine.disease ,Vascular Endothelial Growth Factor Receptor-2 ,Neoplasm Proteins ,Cell biology ,Vascular endothelial growth factor ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Hypoxia-inducible factors ,chemistry ,Connective Tissue ,030220 oncology & carcinogenesis ,Fell‐Muir ,Signal Transduction - Abstract
Studies of proliferative hemangiomas have led to the discovery that interactions of endothelial cells with extracellular matrix and/or Vascular Endothelial Growth Factor (VEGF)‐A stimulate the expression of VEGFR1, the VEGF decoy receptor, and suppress VEGF‐dependent VEGFR2 signalling by a mechanism that requires the matrix‐binding receptor Anthrax Toxin Receptor (ANTXR)1, VEGFR2, β1 integrin and the Nuclear Factor of Activated T cells (NFAT). In hemangioma endothelial cells, all these components are present, but are functionally compromised, so that the levels of VEGFR1 are extremely low and VEGFR2 signalling is constitutively active. Consequently, the levels of Hypoxia Inducible Factor (HIF)‐1α and its transcriptional targets, VEGF‐A and C‐X‐C motif chemokine 12 (CxCl12), are elevated and a positive VEGF‐A feedback loop is established. Overexpression of ANTXR1, carrying a heterozygous Ala‐to‐Thr mutation, induces hemangioma‐like signalling in control endothelial cells; VEGF signalling is normalized when wild‐type ANTXR1 is overexpressed in hemangioma cells. These findings suggest that ANTXR1 functions as a negative regulator of VEGF‐A signalling. Studies of a mouse model of the Growth Retardation, Alopecia, Pseudo‐anodontia and Optic Atrophy (GAPO) syndrome, caused by the loss‐of‐function mutations in ANTXR1, as well as knock‐in mice carrying the Ala‐to‐Thr ANTXR1 mutation, confirm that ANTXR1 functions as a suppressor of VEGF‐A signalling. Cutaneous endothelial cells isolated from ANTXR1‐deficient mice exhibit low levels of VEGFR1, elevated levels of VEGF‐A, HIF‐1α and CxCl12 and activated VEGFR2 signalling as in hemangioma. Increased numbers of myeloid cells in the skin of ANTXR1‐deficient mice are associated with reduced vascularity and increased skin fibrosis, suggesting a mechanism for hemangioma involution and replacement by fibrotic scars. Through controlling VEGF‐A signalling and extracellular matrix synthesis, ANTXR1 is emerging as a key regulator of skeletal and connective tissue development and homeostasis.
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- 2016
5. Targeting VEGF and Its Receptors for the Treatment of Osteoarthritis and Associated Pain
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Bjorn R. Olsen, Masashi Nagao, Di Chen, Hee Jeong Im, Brett R. Levine, and John L. Hamilton
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Angiogenesis ,business.industry ,Endocrinology, Diabetes and Metabolism ,Osteoarthritis ,medicine.disease ,Vascular endothelial growth factor ,Vascular endothelial growth factor B ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,Vascular endothelial growth factor C ,chemistry ,Internal medicine ,Synovitis ,medicine ,Adjuvant therapy ,Orthopedics and Sports Medicine ,Growth factor receptor inhibitor ,business - Abstract
Increased vascular endothelial growth factor (VEGF) levels are associated with osteoarthritis (OA) progression. Indeed, VEGF appears to be involved in OA-specific pathologies including cartilage degeneration, osteophyte formation, subchondral bone cysts and sclerosis, synovitis, and pain. Moreover, a wide range of studies suggest that inhibition of VEGF signaling reduces OA progression. This review highlights both the potential significance of VEGF in OA pathology and pain, as well as potential benefits of inhibition of VEGF and its receptors as an OA treatment. With the emergence of the clinical use of anti-VEGF therapy outside of OA, both as high-dose systemic treatments and low-dose local treatments, these particular therapies are now more widely understood. Currently, there is no established disease-modifying drug available for patients with OA, which warrants continued study of the inhibition of VEGF signaling in OA, as stand-alone or adjuvant therapy. © 2016 American Society for Bone and Mineral Research.
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- 2016
6. A newAdamts9conditional mouse allele identifies its non-redundant role in interdigital web regression
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Brittany Matuska, Hannah L. Bader, Negin Katebi, Johanne Dubail, Bjorn R. Olsen, Noriko Aramaki-Hattori, Suneel S. Apte, and Courtney M. Nelson
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Genetics ,endocrine system ,Mesoderm ,Cre recombinase ,Cell Biology ,Biology ,Penetrance ,Phenotype ,White (mutation) ,Endocrinology ,medicine.anatomical_structure ,medicine ,Allele ,Haploinsufficiency ,Gene knockout - Abstract
ADAMTS9 is the most conserved member of a large family of secreted metalloproteases having diverse functions. Adamts9 null mice die before gastrulation, precluding investigations of its roles later in embryogenesis, in adult mice or disease models. We therefore generated a floxed Adamts9 allele to bypass embryonic lethality. In this mutant, unidirectional loxP sites flank exons 5-8, which encode the catalytic domain, including the protease active site. Mice homozygous for the floxed allele were viable, lacked an overt phenotype, and were fertile. Conversely, mice homozygous for a germ-line deletion produced from the floxed allele by Cre-lox recombination did not survive past gastrulation. Hemizygosity of the deleted Adamts9 in combination with mutant Adamts20 led to cleft palate and severe white spotting as previously described. Previously, Adamts9 haploinsufficiency combined with either Adamts20 or Adamts5 nullizygosity suggested a cooperative role in interdigital web regression, but the outcome of deletion of Adamts9 alone remained unknown. Here, Adamts9 was conditionally deleted in limb mesoderm using Prx1-Cre mice. Unlike other ADAMTS single knockouts, limb-specific Adamts9 deletion resulted in soft-tissue syndactyly (STS) with 100% penetrance and concurrent deletion of Adamts5 increased the severity of STS. Thus, Adamts9 has both non-redundant and cooperative roles in ensuring interdigital web regression. This new allele will be useful for investigating other biological functions of ADAMTS9.
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- 2014
7. Quinolone-resistantEscherichia coliisolated from birds of prey in Portugal are genetically distinct from those isolated from water environments and gulls in Portugal, Spain and Sweden
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Jana Vredenburg, Stefan Bertilsson, Johan Stedt, Carlos Narciso-da-Rocha, Ana Varela, Célia M. Manaia, Badrul Hasan, Jonas Bonnedahl, Bjorn R. Olsen, and Paulo Martins da Costa
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0303 health sciences ,Molecular epidemiology ,030306 microbiology ,Ecology ,medicine.drug_class ,biochemical phenomena, metabolism, and nutrition ,Biology ,bacterial infections and mycoses ,medicine.disease_cause ,Quinolone ,Microbiology ,Predation ,Ciprofloxacin ,Geographic distribution ,03 medical and health sciences ,Habitat ,medicine ,Escherichia coli ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,medicine.drug - Abstract
The influence of geographic distribution and type of habitat on the molecular epidemiology of ciprofloxacin resistant Escherichia coli was investigated. Ciprofloxacin resistant E. coli from wastewa ...
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- 2013
8. Basement membrane molecule expression attendant to chondrogenesis by nucleus pulposus cells and mesenchymal stem cells
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Casper Bindzus Foldager, Bjorn R. Olsen, Myron Spector, and Wei Seong Toh
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Basement membrane ,biology ,Chemistry ,Cellular differentiation ,Mesenchymal stem cell ,Type II collagen ,Chondrogenesis ,Cell biology ,Type IV collagen ,medicine.anatomical_structure ,Tissue engineering ,Laminin ,Immunology ,medicine ,biology.protein ,Orthopedics and Sports Medicine - Abstract
Bone marrow-derived mesenchymal stem cells (MSCs) represent an autologous cell source for nucleus pulposus (NP) tissue engineering and regeneration. Although studies have demonstrated the ability of MSCs to differentiate to NP-like chondrocytic cells, few have comparatively studied the matrix synthesis and composition of the cartilaginous tissue formed in vitro from both cell types, particularly with respect to the expression of basement membrane (BM) molecules. The objective of this study was to evaluate chondrogenesis and expression of BM molecules, laminin and type IV collagen, in monolayer and in pellet cultures of caprine NP cells and MSCs. Both cell types demonstrated comparable levels of chondrogenesis, indicated by the percentage of chondrocytic cells, and the amounts of glycosaminoglycan and type II collagen. Laminin and type IV collagen were expressed intracellularly by NP cells and MSCs cultured in monolayer. During chondrogenesis in pellet cultures, the deposition of BM molecules in NP and MSC pellets followed an orderly spatiotemporal shift in pattern from a diffuse territorial and interterritorial distribution to a defined pericellular localization, as seen in normal adult NP. These results inform the use of MSCs for NP regeneration and suggest the possible involvement of certain BM molecules in chondrogenesis and cartilage regeneration.
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- 2013
9. Prevalence of extended-spectrum beta-lactamase-producingEnterobacteriaceaein healthy Swedish preschool children
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Åsa Melhus, Ylva Molin, Johan Kaarme, and Bjorn R. Olsen
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Male ,Pediatrics ,medicine.medical_specialty ,medicine.medical_treatment ,beta-Lactamases ,Feces ,Enterobacteriaceae ,Epidemiology ,Genotype ,Prevalence ,polycyclic compounds ,medicine ,Humans ,Prospective Studies ,Typing ,Child ,Escherichia coli Infections ,Sweden ,biology ,business.industry ,Infant ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,University hospital ,biology.organism_classification ,Anti-Bacterial Agents ,Carriage ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Beta-lactamase ,Female ,business - Abstract
Aim The objective was to determine the prevalence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in faeces from healthy Swedish preschool children and to establish whether transmission took place between children in preschools. Methods Diapers from children attending preschools in Uppsala city were collected during September to October 2010, and the faeces was cultured. Antibiotic profiles and carriage of CTX-M, TEM, SHV and AmpC type enzymes were determined. PCR-positive isolates were further characterized by sequencing and epidemiological typing. Statistics on antibiotic use and ESBL producers in paediatric patients at Uppsala University Hospital were extracted for comparison. Results A total of 313 stool specimens were obtained, representing 24.5% of all preschool children in Uppsala city. The carriage rate of ESBL-producing Enterobacteriaceae was 2.9% among these healthy children. The corresponding figure for patients in the same age group was 8.4%. Escherichia coli with CTX-M type enzymes predominated, and only one E. coli isolate carried genes-encoding CMY. CTX-M-producing E. coli isolates with identical genotypes were found in children with no familial relation at two different preschools. Conclusions Using diapers, the prevalence of ESBL-producing Enterobacteriaceae in children was quickly established, and, most likely, a transmission of ESBL-producing E. coli was for the first time documented between children at the same preschool.
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- 2013
10. The mouse palate and its cellular responses to midpalatal suture expansion forces
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Negin Katebi, Elona Kolpakova-Hart, Bjorn R. Olsen, and C. Y. Lin
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Periosteum ,Collagen ii ,Extramural ,business.industry ,Orthodontics ,Anatomy ,Mechanical force ,medicine.anatomical_structure ,Otorhinolaryngology ,Cranial sutures ,Medicine ,Surgery ,Palatal Expansion Technique ,Oral Surgery ,Midpalatal suture ,business - Abstract
Objectives To investigate the anatomy of the mouse palate, the midpalatal suture, and the cellular characteristics in the sutures before and immediately after midpalatal suture expansion.
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- 2012
11. WITHDRAWN; Recent progress in studies of infantile hemangioma
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Eileen Boye, Masatoshi Jinnin, Tsuyoshi Ishihara, and Bjorn R. Olsen
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Pathology ,medicine.medical_specialty ,VEGF receptors ,Normal tissue ,Dermatology ,General Medicine ,Biology ,medicine.disease ,Vascular endothelial growth factor ,Hemangioma ,Pathogenesis ,chemistry.chemical_compound ,chemistry ,Multipotent Stem Cell ,Infantile hemangioma ,medicine ,biology.protein ,Involution (medicine) - Abstract
A hallmark of infantile hemangioma, the most common tumor of infancy, is its dramatic growth after birth, by diffuse proliferation of immature endothelial cells, followed by spontaneous regression. The growth and involution of infantile hemangioma is quite different from other vascular anomalies, which do not regress and can occur at any time during life. Some hemangioma lesions can be extremely disfiguring and destructive to normal tissue and may even be life-threatening. Unfortunately, existing therapeutic approaches have limited success and significant adverse effects of some treatment modalities limit their use. Better understanding of the pathogenesis of hemangioma will enable the development of better therapeutic strategies. Herein, we review recent studies and new hypotheses on the pathogenesis of the tumor. Detailed mechanisms of activated vascular endothelial growth factor (VEGF) signaling in tumor cells, identification of their origin and characterization of multipotent stem cells that can give rise to infantile hemangioma are shedding new light on this intriguing vascular tumor.
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- 2010
12. Recent progress in studies of infantile hemangioma
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Eileen Boye, Masatoshi Jinnin, Tsuyoshi Ishihara, and Bjorn R. Olsen
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Male ,Pathology ,medicine.medical_specialty ,Skin Neoplasms ,medicine.medical_treatment ,Dermatology ,Biology ,Pathogenesis ,Hemangioma ,chemistry.chemical_compound ,medicine ,Vascular Neoplasm ,Humans ,Involution (medicine) ,Vascular Endothelial Growth Factors ,Stem Cells ,Infant, Newborn ,Infant ,General Medicine ,medicine.disease ,Vascular Neoplasms ,Vascular endothelial growth factor ,Receptors, Vascular Endothelial Growth Factor ,Cytokine ,chemistry ,Head and Neck Neoplasms ,Multipotent Stem Cell ,Female ,Endothelium, Vascular ,Stem cell ,Signal Transduction - Abstract
A hallmark of infantile hemangioma, the most common tumor of infancy, is its dramatic growth after birth, by diffuse proliferation of immature endothelial cells, followed by spontaneous regression. The growth and involution of infantile hemangioma is quite different from other vascular anomalies, which do not regress and can occur at any time during life. Some hemangioma lesions can be extremely disfiguring and destructive to normal tissue and may even be life-threatening. Unfortunately, existing therapeutic approaches have limited success and significant adverse effects of some treatment modalities limit their use. Better understanding of the pathogenesis of hemangioma will enable the development of better therapeutic strategies. Herein, we review recent studies and new hypotheses on the pathogenesis of the tumor. Detailed mechanisms of activated vascular endothelial growth factor (VEGF) signaling in tumor cells, identification of their origin and characterization of multipotent stem cells that can give rise to infantile hemangioma are shedding new light on this intriguing vascular tumor.
- Published
- 2010
13. A novel Chlamydiaceae-like bacterium found in faecal specimens from sea birds from the Bering Sea
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Jonas Waldenström, Mikael Thollesson, Ingvar Eliasson, Linus Christerson, Björn Herrmann, Karin Grannas, Maria Blomqvist, Karine Laroucau, and Bjorn R. Olsen
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Chlamydophila ,Chlamydia ,biology ,macromolecular substances ,bacterial infections and mycoses ,urologic and male genital diseases ,biology.organism_classification ,medicine.disease ,medicine.disease_cause ,Agricultural and Biological Sciences (miscellaneous) ,female genital diseases and pregnancy complications ,Microbiology ,FAMILY CHLAMYDIACEAE ,medicine ,Chlamydiaceae ,Chlamydia trachomatis ,Biological sciences ,Ecology, Evolution, Behavior and Systematics ,Bacteria - Abstract
The family Chlamydiaceae contains several bacterial pathogens of important human and veterinary medical concern, such as Chlamydia trachomatis and Chlamydophila psittaci. Within the order Chlamydia ...
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- 2010
14. Endogenous endostatin inhibits choroidal neovascularization
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Alexander G. Marneros, Haicheng She, Edward Connolly, Bjorn R. Olsen, Hiroya Hashizume, Ivana K. Kim, Joan W. Miller, Hadi J. Zambarakji, and Evangelos S. Gragoudas
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Male ,genetic structures ,Angiogenesis ,Endogeny ,macromolecular substances ,Biochemistry ,Bruch's membrane ,Pichia ,Capillary Permeability ,Pathogenesis ,Macular Degeneration ,Mice ,In vivo ,Genetics ,medicine ,Animals ,Humans ,Molecular Biology ,Mice, Knockout ,Basement membrane ,Choroid ,business.industry ,Membrane Proteins ,Fluoresceins ,Choroidal Neovascularization ,Recombinant Proteins ,eye diseases ,Collagen Type XVIII ,Endostatins ,Rats ,Mice, Inbred C57BL ,Choroidal neovascularization ,medicine.anatomical_structure ,cardiovascular system ,Cancer research ,Female ,Bruch Membrane ,sense organs ,medicine.symptom ,Endostatin ,business ,Biotechnology - Abstract
Endostatin, a fragment of the basement membrane component collagen XVIII, exhibits antiangiogenic properties in vitro and in vivo when high doses are administered. It is not known whether endogenous endostatin at physiological levels has a protective role as an inhibitor of pathological angiogenesis, such as choroidal neovascularization (CNV) in age-related macular degeneration. Using a laser injury model, we induced CNV in mice lacking collagen XVIII/endostatin and in control mice. CNV lesions in mutant mice were approximately 3-fold larger than in control mice and showed increased vascular leakage. These differences were independent of age-related changes at the choroid-retina interface. Ultrastructural analysis of the choroidal vasculature in mutant mice excluded morphological vascular abnormalities as a cause for the larger CNV lesions. When recombinant endostatin was administered to collagen XVIII/endostatin-deficient mice, CNV lesions were similar to those seen in control mice. In control mice treated with recombinant endostatin, CNV lesions were almost undetectable. These findings demonstrate that endogenous endostatin is an inhibitor of induced angiogenesis and that administration of endostatin potently inhibits CNV growth and vascular leakage. Endostatin may have a regulatory role in the pathogenesis of CNV and could be used therapeutically to inhibit growth and leakage of CNV lesions.
- Published
- 2007
15. Targeted disruption ofCol8a1andCol8a2genes in mice leads to anterior segment abnormalities in the eye
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En Li, Naomi Fukai, Gunter Wolf, Helmut Hopfer, Ulrike Hopfer, Nancy C. Joyce, and Bjorn R. Olsen
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Male ,Corneal endothelium ,genetic structures ,Collagen Type VIII ,Biology ,Biochemistry ,Cornea ,Mice ,Dysgenesis ,Stroma ,Anterior Eye Segment ,Genetics ,medicine ,Extracellular ,Animals ,Eye Abnormalities ,Molecular Biology ,Aorta ,Cell Proliferation ,Basement membrane ,Endothelium, Corneal ,Gene Expression Regulation, Developmental ,Anatomy ,eye diseases ,Cell biology ,Mice, Inbred C57BL ,Collagen, type I, alpha 1 ,medicine.anatomical_structure ,Membrane ,Eye development ,Female ,sense organs ,Biotechnology - Abstract
Collagen VIII is localized in subendothelial and subepithelial extracellular matrices. It is a major component of Descemet's membrane, a thick basement membrane under the corneal endothelium, where it forms a hexagonal lattice structure; a similar structure, albeit less extensive, may be formed in other basement membranes. We have examined the function of collagen VIII in mice by targeted inactivation of the genes encoding the two polypeptide subunits, Col8a1 and Col8a2. Analysis of these mice reveals no major structural defects in most organs, but demonstrates that type VIII collagen is required for normal anterior eye development, particularly the formation of a corneal stroma with the appropriate number of fibroblastic cell layers and Descemet's membrane of appropriate thickness. Complete lack of type VIII collagen leads to dysgenesis of the anterior segment of the eye: a globoid, keratoglobus-like protrusion of the anterior chamber with a thin corneal stroma. Descemet's membrane is markedly thinned. The corneal endothelial cells are enlarged and reduced in number, and show a decreased ability to proliferate in response to different growth factors in vitro. An important function of collagen VIII may therefore be to generate a peri- or subcellular matrix environment that permits or stimulates cell proliferation.
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- 2005
16. Physiological role of collagen XVIII and endostatin
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Bjorn R. Olsen and Alexander G. Marneros
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Aging ,Iris ,Neovascularization, Physiologic ,Blindness ,Cleavage (embryo) ,Biochemistry ,Basement Membrane ,Retina ,Mice ,Genetics ,Collagen Type XVIII ,medicine ,Animals ,Humans ,Collagen XVIII ,Pigment Epithelium of Eye ,Molecular Biology ,Encephalocele ,Mice, Knockout ,Basement membrane ,biology ,Chemistry ,Ciliary Body ,Retinal Degeneration ,digestive, oral, and skin physiology ,Retinal Vessels ,Syndrome ,Endostatins ,Cell biology ,stomatognathic diseases ,Collagen, type I, alpha 1 ,medicine.anatomical_structure ,Membrane ,Proteoglycan ,Mutation ,Immunology ,biology.protein ,Heparitin Sulfate ,Laminin ,Endostatin ,Heparan Sulfate Proteoglycans ,Biotechnology - Abstract
Collagen XVIII is a component of basement membranes (BMs) with the structural properties of both a collagen and a proteoglycan. Proteolytic cleavage within its C-terminal domain releases a fragment, endostatin, which has been reported to have anti-angiogenesis effects. Molecular studies demonstrated binding of the endostatin domain to heparan sulfate and to BM components like laminin and perlecan, but the functional role of these interactions in vivo remains unknown. Insights into the physiological function of collagen XVIII/endostatin have recently been obtained through the identification of inactivating mutations in the human collagen XVIII/endostatin gene (COL18A1) in patients with Knobloch syndrome, characterized by age-dependent vitreoretinal degeneration and occipital encephalocele. That collagen XVIII/endostatin has an essential role in ocular development and the maintenance of visual function is further demonstrated by the ocular abnormalities seen in mice lacking collagen XVIII/endostatin. Age-dependent loss of vision in these mutant mice is associated with pathological accumulation of deposits under the retinal pigment epithelium, as seen in early stages of age-related macular degeneration in humans. In addition, recent evidence suggests that lack of collagen XVIII/endostatin predisposes to hydrocephalus formation. These recent findings demonstrate an important role for collagen XVIII/endostatin in cell-matrix interactions in certain tissues that may be compensated for in other tissues expressing this collagen.
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- 2005
17. Comparison of the NH2-Terminal Sequences of Chick Type I Preprocollagen Chains Synthesized in an mRNA-Dependent Reticulocyte Lysate
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Bjorn R. Olsen, Peter N. Graves, Darwin J. Prockop, Peter P. Fietzek, and Janet M. Monson
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Reticulocytes ,Lysis ,Sequence (biology) ,Peptide ,Chick Embryo ,Biology ,Biochemistry ,Reticulocyte ,medicine ,Animals ,Trypsin ,Amino Acid Sequence ,RNA, Messenger ,Protein Precursors ,chemistry.chemical_classification ,Messenger RNA ,RNA ,Translation (biology) ,Embryo ,Molecular biology ,Molecular Weight ,Cartilage ,Microbial Collagenase ,medicine.anatomical_structure ,chemistry ,Protein Biosynthesis ,Collagen ,Rabbits ,Procollagen - Abstract
RNA was extracted from 17-day-old chick embryo calvaria and translated by an mRNA-dependent reticulocyte lysate. Procedures were developed for purifying intact pro alpha 1(I) and pro alpha 2 translation products from the lysate. These products were identified by comparing tryptic peptide elution patterns of the translation products with those obtained from secreted pro alpha chains. Partial sequence data from the amino terminus of each translation product demonstrated that each chain begins with a sequence that is different from that of the corresponding pro alpha chain, and that the two sequences are not the same. Also, the bacterial collagenase-resistant peptide from the amino terminus of prepro alpha 1(I) had an apparent molecular weight which was 10 000 greater than the peptide from pro alpha 1(I).
- Published
- 2005
18. Strategies for Directing the Differentiation of Stem Cells Into the Osteogenic Lineage In Vitro
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Bjorn R. Olsen, Paul Robson, Lawrence W. Stanton, Boon Chin Heng, and Tong Cao
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Lineage (genetic) ,Stem Cells ,Endocrinology, Diabetes and Metabolism ,Cellular differentiation ,Cell Culture Techniques ,Clinical uses of mesenchymal stem cells ,Cell Differentiation ,Biology ,Osteocytes ,Regenerative medicine ,Embryonic stem cell ,In vitro ,Cell biology ,Transplantation ,Osteogenesis ,Immunology ,Animals ,Humans ,Orthopedics and Sports Medicine ,Stem cell ,Stem Cell Transplantation - Abstract
A major area in regenerative medicine is the application of stem cells in bone reconstruction and bone tissue engineering. This will require well-defined and efficient protocols for directing the differentiation of stem cells into the osteogenic lineage, followed by their selective purification and proliferation in vitro. The development of such protocols would reduce the likelihood of spontaneous differentiation of stem cells into divergent lineages on transplantation, as well as reduce the risk of teratoma formation in the case of embryonic stem cells. Additionally, such protocols could provide useful in vitro models for studying osteogenesis and bone development, and facilitate the genetic manipulation of stem cells for therapeutic applications. The development of pharmokinetic and cytotoxicity/genotoxicity screening tests for bone-related biomaterials and drugs could also use protocols developed for the osteogenic differentiation of stem cells. This review critically examines the various strategies that could be used to direct the differentiation of stem cells into the osteogenic lineage in vitro.
- Published
- 2004
19. Laser capture microdissection (LCM) for analysis of gene expression in specific tissues during embryonic epithelial-mesenchymal transformation
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Damian LaGamba, Bjorn R. Olsen, Ali Nawshad, and Elizabeth D. Hay
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Lymphoid Enhancer-Binding Factor 1 ,Gene Expression ,Biology ,Epithelium ,law.invention ,Mesoderm ,Mice ,law ,Gene expression ,Animals ,RNA, Messenger ,Gene ,Polymerase chain reaction ,Laser capture microdissection ,Messenger RNA ,Palate ,Reverse Transcriptase Polymerase Chain Reaction ,Lasers ,Mesenchymal stem cell ,Embryo, Mammalian ,Embryonic stem cell ,Molecular biology ,DNA-Binding Proteins ,Transformation (genetics) ,Organ Specificity ,Microdissection ,Transcription Factors ,Developmental Biology - Abstract
The analysis of gene expression in developing organs is a valuable tool for the assessment of genetic fingerprints during the various stages of tissue differentiation and epithelial-mesenchymal transformation (EMT). However, the variety of differentiating cells and the close association of epithelial and mesenchymal cells makes it difficult to extract protein and mRNA from specific cells and tissue and, thus, to assign expressed genes to specific cell populations. We report here the analysis of LEF1 mRNA in epithelial and mesenchymal cells isolated by LCM from different stages of EMT during development of the mouse palate and describe our techniques in detail. By applying a laser capture microdissection (LCM) technique and real-time polymerase chain reaction, we were able to determine mRNA levels that accurately reflect changes in gene expression in specific cells. The sensitivity of the technique is remarkable. Indeed, the mRNAs can be detected for many proteins too low in abundance to stain with antibodies. These techniques will enable embryologists to collect homogeneous groups of cells from heterogeneous populations in developing organs, which otherwise would not be available for gene analysis.
- Published
- 2004
20. Directed Differentiation of Human Embryonic Stem Cells to Neural Crest Stem Cells, Functional Peripheral Neurons, and Corneal Keratocytes
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Chaminda Jayampath Seneviratne, Tong Cao, Mengfei Yu, Bjorn R. Olsen, Mingming Li, Huei Jinn Tong, Chuan Yan, Gopu Sriram, Qian Zhu, Qiqi Lu, Walter Hunziker, Rong Gao, Shunhui Wei, Yu Zou, and Zhiyuan Gong
- Subjects
0301 basic medicine ,Embryo, Nonmammalian ,Neurogenesis ,Human Embryonic Stem Cells ,Population ,Cell Culture Techniques ,Corneal Keratocytes ,Biology ,Applied Microbiology and Biotechnology ,03 medical and health sciences ,Directed differentiation ,Neural Stem Cells ,Animals ,Humans ,CD90 ,education ,Cells, Cultured ,Zebrafish ,Neurons ,education.field_of_study ,Neuroectoderm ,Mesenchymal stem cell ,Neural crest ,General Medicine ,Anatomy ,Flow Cytometry ,Embryonic stem cell ,Cell biology ,030104 developmental biology ,Neural Crest ,embryonic structures ,Molecular Medicine ,sense organs ,Stem cell - Abstract
Neural crest stem cells (NCSCs) are a transient and multipotent cell population giving rise to various cell types with clinical importance. Isolation of human NCSCs is extremely challenging that limits our knowledge about neural crest development and application. Here, a defined protocol to efficiently direct human embryonic stem cells (hESCs) to NCSCs and multiple neural crest lineages is presented. A unique combination of small molecule inhibitors and growth factors is employed to generate NCSCs from hESCs through a neuroectoderm stage. The self-renewal and multipotent capacities of hESC-derived NCSCs are assessed subsequently. In the feeder-free system, hESC-derived NCSCs (P75+ /HNK1+ /AP2α+ /PAX6- ) in high purity are efficiently generated following neuroectodermal restriction. They can be propagated and differentiated toward multiple neural crest lineages in vitro, such as functional peripheral neurons (β-tubulin III+ /peripherin+ ), mesenchymal stem cells (CD73+ CD90+ CD105+ ), and corneal keratocytes (keratocan+ ). The in vivo developmental potential of hESC-derived NCSCs is confirmed using zebrafish embryos. This report is the first demonstration of efficient differentiation of hESCs into corneal keratocytes as a monolayer in a feeder-free system. Considering the high efficacy of NCSC generation, this new method will be a useful tool for future clinical organ repair and regeneration, such as peripheral nerve regeneration and corneal repair.
- Published
- 2017
21. Teratology Society platform sessions abstracts
- Author
-
Bjorn R. Olsen, I.G. Lavrin, Robert E. Seegmiller, E.D. Hay, C.W. Archer, and William McLean
- Subjects
Embryology ,Chemistry ,Health, Toxicology and Mutagenesis ,Toxicology ,Mechanism (sociology) ,Developmental Biology ,Cell biology - Published
- 2000
22. Identification of multiple loci linked to inflammation and autoantibody production by a genome scan of a murine model of rheumatoid arthritis
- Author
-
Jill T. Enders, Jeffrey M. Otto, Yefu Li, Edit I. Buzás, Gabriella Cs-Szabo, Sonja Velins, Tibor T. Glant, Bjorn R. Olsen, Katalin Mikecz, and Jodi Gallagher
- Subjects
Genetics ,Chromosome 7 (human) ,Immunology ,Haplotype ,Autoantibody ,food and beverages ,Arthritis ,Locus (genetics) ,Biology ,Quantitative trait locus ,medicine.disease ,Chromosome 15 ,Rheumatology ,Genetic marker ,medicine ,Immunology and Allergy ,Pharmacology (medical) - Abstract
Objective Proteoglycan-induced arthritis (PGIA) is a murine model of rheumatoid arthritis (RA), both in terms of its pathology and its genetics. PGIA can only be induced in susceptible murine strains and their F2 progeny. As with RA, the genetics are complex, containing both major histocompatibility complex (MHC)–related and non–MHC-related components. Our goal was to identify the underlying non–MHC-related loci that confer PGIA susceptibility. Methods We used 106 polymorphic markers to perform simple sequence-length polymorphism analysis on F2 hybrids of susceptible (BALB/c) and nonsusceptible (DBA/2) strains of mice. Because both strains of mice share the H2d haplotype, this cross permits identification and analysis of non–MHC-related genes. Results We identified a total of 12 separate quantitative trait loci (QTL) associated with PGIA, which we have named Pgia1 through Pgia12. QTLs associated with the inflammatory symptoms of PGIA were linked to chromosomes 7, 9, 15 (2 separate loci), 16, and 19. QTLs associated with autoantibody production were identified on chromosomes 1, 2, 7, 8, 10, 11, 16, and 18. QTLs on chromosomes 7 and 16 showed linkage to both inflammation and autoantibody production, suggesting a shared regulatory component in arthritis induction. The first inflammation QTL on chromosome 15 and the autoantibody QTL on chromosome 7 originate from the DBA/2 background, which indicates that as in RA, susceptibility genes can originate from heterogeneous backgrounds. Conclusion These data demonstrate the complexity of PGIA, where QTLs may be involved in multiple traits or even originate from a genetic background previously determined to be resistant.
- Published
- 1999
23. Endostatin inhibits VEGF-induced endothelial cell migration and tumor growth independently of zinc binding
- Author
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Robert Shapiro, Rupert Timpl, Bela Anand-Apte, Clemens W.G.M. Löwik, Noriko Yamaguchi, Takako Sasaki, Margaret S. Lee, Naomi Fukai, Ivo Que, and Bjorn R. Olsen
- Subjects
Vascular Endothelial Growth Factor A ,Angiogenesis ,Recombinant Fusion Proteins ,Cell ,Mice, Nude ,Type XVIII collagen ,Antineoplastic Agents ,Endothelial Growth Factors ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Umbilical vein ,Mice ,chemistry.chemical_compound ,Cell Movement ,medicine ,Animals ,Humans ,Carcinoma, Renal Cell ,Molecular Biology ,Cells, Cultured ,Cell Line, Transformed ,Lymphokines ,Mice, Inbred BALB C ,Migration Assay ,General Immunology and Microbiology ,Vascular Endothelial Growth Factors ,General Neuroscience ,Molecular biology ,Kidney Neoplasms ,Peptide Fragments ,Endostatins ,Endothelial stem cell ,Vascular endothelial growth factor ,Zinc ,medicine.anatomical_structure ,chemistry ,Mutagenesis ,cardiovascular system ,Collagen ,Endothelium, Vascular ,Endostatin ,Research Article - Abstract
Endostatin, produced as recombinant protein in human 293-EBNA cells, inhibits the migration of human umbilical vein endothelial cells (HUVECs) in response to vascular endothelial growth factor (VEGF) in a dose-dependent manner and prevents the subcutaneous growth of human renal cell carcinomas in nude mice at concentrations and in doses that are from 1000- to 100 000-fold lower than those previously reported. The inhibition of migration is not affected by mutations which eliminate Zn or heparin binding and inhibition of tumor growth does not depend on Zn binding. The results of the migration assays suggest that endostatin causes a block at one or more steps in VEGF-induced migration, while VEGF in turn can cause a block of the inhibition by endostatin of VEGF-induced migration of HUVECs.
- Published
- 1999
24. Mouse clavicular development: Analysis of wild-type and cleidocranial dysplasia mutant mice
- Author
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Paul B. Selby, Bjorn R. Olsen, Stefan Mundlos, Naomi Fukai, and Lih-Fen Huang
- Subjects
Pathology ,medicine.medical_specialty ,biology ,Cartilage ,Mesenchymal stem cell ,Type II collagen ,Autosomal dominant trait ,Anatomy ,medicine.anatomical_structure ,medicine ,biology.protein ,Bone marrow ,Osteopontin ,Endochondral ossification ,Type I collagen ,Developmental Biology - Abstract
Cleidocranial dysplasia (CCD) is an autosomal dominant disease characterized by hypoplasia or aplasia of clavicles, open fontanelles, and other skeletal anomalies. A mouse mutant, shown by clinical and radiographic analysis to be strikingly similar to the human disorder and designated Ccd, was used as a model for the human disorder. Since malformation of the clavicle is the hallmark of CCD, we studied clavicular development in wild-type and Ccd mice. Histology and in situ hybridization experiments were performed to compare the temporal and spatial expression of several genes in wild-type and Ccd mutant mouse embryos. Bone and cartilage specific markers--type I, II, and X collagens, Sox9, aggrecan, and osteopontin were used as probes. The analyses covered the development of the clavicle from the initial mesenchymal condensation at embryonic day 13 (E13) to the late mineralization stage at embryonic day 15.5. At day 13.5, cells in the center of the condensation differentiate into characteristic precursor cells that were not observed in other bone anlagen. In the medial part of the anlage these cells express markers of the early cartilage lineage (type II collagen and Sox9), whereas cells of the lateral part express markers of the osteoblast lineage (type I collagen). With further development the medial cells differentiate into chondrocytes and start to express chondrocyte-specific markers such as aggrecan. Cells of the lateral part differentiate into osteoblasts as indicated by the production of bone matrix and the expression of osteopontin. At day 14.5 a regular growth plate has developed between the two parts where type X collagen expression can be demonstrated in hypertrophic chondrocytes. The data indicate that the medial part of the clavicle develops by endochondral bone formation while the lateral part ossifies as a membranous bone. The clavicle of Ccd mice showed a smaller band of mesenchymal cell condensation than in wild-type mice. Cells of the condensation failed to express type I and type II collagen at E13.5. In the lateral part of the clavicle type I collagen expression was not detected until E14.5 and osteopontin expression only appeared at E15.5. At E15.5, a small ossification center appears in the lateral part which is, in contrast to the wild-type clavicular bone, solid and without primary spongiosa as well as bone marrow. In the medial portion, type II collagen expression and endochondral ossification never occurs in Ccd mice; this portion of the clavicle is therefore missing in Ccd.
- Published
- 1997
25. Craniofacial abnormalities in mice carrying a dominant interference mutation in type X collagen
- Author
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Bjorn R. Olsen, Kun Sung Chung, Ichiro Nishimura, Patrick M. Boyle, and Olena Jacenko
- Subjects
Genetically modified mouse ,Pathology ,medicine.medical_specialty ,Craniofacial abnormality ,Cartilage ,Anatomy ,Biology ,medicine.disease ,Condyle ,Collagen, type I, alpha 1 ,medicine.anatomical_structure ,medicine ,Immunohistochemistry ,Craniofacial ,Endochondral ossification ,Developmental Biology - Abstract
Type X collagen is a short, non-fibril forming collagen restricted to hypertrophic cartilage, and has been hypothesized to play a role in endochondral ossification. The purpose of the study was to investigate the consequences resulting from the interference of type X collagen function on the growth and development of the craniofacial skeleton through analysis of transgenic mice with a dominant interference mutation for type X collagen. The craniofacial tissues of 21-day-old transgenic mice were examined by: cephalometric and radiographic densitometry analyses, conventional histology, and immunohistochemistry using antibodies specific for either endogenous mouse type X collagen or the transgene product. Genotypically positive mutant mice showed moderate but statistically significant craniofacial skeletal abnormalities, including the underdevelopment of the chondrocranium and mandible, but no cleft palate. Mean radiographic optical densities of the mutant condylar cartilage and the subchondylar areas were 32% less than the corresponding areas of normal mandibles, while mean radiographic optical density measured at the incisor tooth point remained constant. Histologically, transgene-positive mice revealed compressed hypertrophic cartilage zones and reduced trabeculae in both the mandibular condyle and the synchondroses of the chondrocranium. In the normal condyle, mouse type X collagen was localized by the monospecific antibody against a synthetic rat type X collagen NC1 peptide throughout the hypertrophic cartilage layer; in the mutant condyle, immunoreactivity to endogenous type X collagen was only seen sporadically. The truncated type X collagen transgene product, identified with the monoclonal antibody against an epitope within the chick type X collagen NC2 domain, persisted in the lower hypertrophic cartilage layer and the primary spongiosa, rather than being removed by subsequent endochondral ossification. The data suggested that the expression of the chick type X collagen transgene product was strongly associated with the craniofacial skeletal abnormalities that were distinct from other cartilage-related phenotypes.
- Published
- 1997
26. Heritable diseases of the skeleton. Part II: Molecular insights into skeletal development‐matrix components and their homeostasis
- Author
-
Bjorn R. Olsen and Stefan Mundlos
- Subjects
Cartilage oligomeric matrix protein ,Mutation ,biology ,Cartilage ,Physiology ,Matrix (biology) ,medicine.disease_cause ,Biochemistry ,Sulfate transport ,Cell biology ,Extracellular matrix ,medicine.anatomical_structure ,Genetics ,biology.protein ,medicine ,Molecular Biology ,Gene ,Aggrecan ,Biotechnology - Abstract
A range of osteochondrodysplasias is caused by mutations in components of the extracellular matrix in cartilage and bone and in molecules that are important for posttranslational processing of such components. Mutations in the genes encoding the two polypeptide subunits of collagen I cause defects in the structure of bone matrix while mutations in genes encoding cartilage-specific collagens are responsible for several chondrodysplasias. Abnormalities in cartilage structure and function can also be due to mutations in structural noncollagenous components such as aggrecan and cartilage oligomeric matrix protein. Finally, several cartilage and bone disorders are due to abnormalities in sulfate transport and regulation of bone matrix homeostasis.
- Published
- 1997
27. Heritable diseases of the skeleton. Part I: Molecular insights into skeletal development‐transcription factors and signaling pathways 1
- Author
-
Bjorn R. Olsen and Stefan Mundlos
- Subjects
Cartilage ,Mesenchymal stem cell ,Biology ,Fibroblast growth factor ,Biochemistry ,Chondrocyte ,Cell biology ,medicine.anatomical_structure ,Fibroblast growth factor receptor ,Intramembranous ossification ,Genetics ,medicine ,Molecular Biology ,Endochondral ossification ,Transcription factor ,Biotechnology - Abstract
The recent identification of the genetic basis of hereditary skeletal disorders is providing important insights into the intricate processes of skeletal formation, growth, and homeostasis. These processes include patterning events during condensation and differentiation of mesenchymal cells to form cartilage precursors of the future bones, the replacement of cartilage by bones through endochondral ossification, the growth of long bones through proliferation and differentiation of chondrocytes in growth plates, and bone formation through differentiation of osteoblasts from mesenchymal cells in areas of intramembranous ossification. Defects in any of these processes can give rise to skeletal abnormalities. Mutations in transcription factors such as HOX and PAX and members of the transforming growth factor-beta superfamily cause disorders associated with abnormal mesenchymal condensation, whereas defects in the transcription factor SOX-9 lead to abnormalities in chondrocyte differentiation. Abnormal growth plate function, resulting in dwarfism, is the consequence of mutations in receptors for fibroblast growth factors and parathyroid hormone-related peptide. Premature closure of cranial sutures in intramembranous ossification is a feature of syndromes due to mutations in fibroblast growth factor receptors.
- Published
- 1997
28. Disproportionate micromelia (Dmm) in mice caused by a mutation in the C-propeptide coding region ofCol2a1
- Author
-
Robert E. Seegmiller, Bjorn R. Olsen, Yefu Li, Cory Teuscher, James M. Pace, and Benjamin A. Taylor
- Subjects
Genetics ,Genetic linkage ,Micromelia ,Mutant ,Type II collagen ,Wild type ,Coding region ,Locus (genetics) ,Biology ,Gene ,Molecular biology ,Developmental Biology - Abstract
Mice that are homozygous for the autosomal semidominant disproportionate micromelia (Dmm) mutation are characterized by disproportionate micromelia, thoracic dysplasia, and cleft palate. Chondrocytes of the epiphyseal growth plates are not organized into columns, and ultrastructural analysis reveals excessive dilation of the endoplasmic reticulum and a paucity of collagen fibrils in the extracellular matrix. To map the Dmm locus, Dmm mice were crossed with the multiple ecotropic viral (MEV) linkage testing stock. Significant linkage of Dmm to the fourteen MEV linkage markers was not observed, thereby excluding approximately 50% of the genome as candidate regions encoding Dmm. Subsequently, microsatellite markers were used to assess linkage to the nonexcluded regions of the genome, revealing tight linkage to the locus of Col2a1, the gene encoding the α-chains of type II collagen. α1(II) collagen cDNA, synthesized with RNA from homozygotes, was cloned and sequenced, revealing a three-nucleotide deletion in the region encoding the C-propeptide globular domain. The deletion leads to the substitution of one amino acid, Asn, in the mutant for two amino acids, Lys and Thr, in the wild type. Several human chondrodysplasias with similar phenotypes to that of Dmm are associated with defects in type II collagen. Thus, mice bearing the Dmm mutation serve as a model for studying the pathogenesis of these disorders while revealing novel insights into normal skeletal morphogenesis. Dev Dyn 208:25–33, 1997. © 1997 Wiley-Liss, Inc.
- Published
- 1997
29. 92-kDa type IV collagenase and TIMP-3, but not 72-kDa type IV collagenase or TIMP-1 or TIMP-2, are highly expressed during mouse embryo implantation
- Author
-
I Thesleff, Bjorn R. Olsen, C Sahlberg, S S Apte, I Leivo, Paula Reponen, and Karl Tryggvason
- Subjects
medicine.medical_specialty ,Stromal cell ,In situ hybridization ,Biology ,Basement Membrane ,Mice ,Internal medicine ,Decidua ,medicine ,Animals ,Collagenases ,Embryo Implantation ,Glycoproteins ,Tissue Inhibitor of Metalloproteinase-3 ,Tissue Inhibitor of Metalloproteinase-2 ,Metalloproteinase ,Metalloendopeptidases ,Proteins ,Trophoblast ,Tissue Inhibitor of Metalloproteinases ,Embryo ,Embryonic Tissue ,Molecular biology ,Decidual reaction ,Extracellular Matrix ,Trophoblasts ,Mice, Inbred C57BL ,Molecular Weight ,Endocrinology ,medicine.anatomical_structure ,Enzyme Induction ,Protein Biosynthesis ,embryonic structures ,Mice, Inbred CBA ,Collagenase ,Female ,Developmental Biology ,medicine.drug - Abstract
Expression of 72 kDa and 92 kDa type IV collagenases and the metalloproteinase inhibitors TIMPs 1, 2, and 3 was studied by in situ hybridization in implanting mouse embryos of days 5.5 to 7.5. The 92 kDa type IV collagenase was strongly expressed in invading trophoblasts, signals above background not being observed in the embryonic proper or placental tissue. In contrast, signals above background were not seen for the 72 kDa enzyme in any cells of the implantation region, including trophoblasts and stromal cells of the decidual tissue. Only cells in the mucosal stroma outside the decidual region displayed some expression. TIMP-3 was intensily expressed in maternal cells in the area surrounding the invading embryonic tissue. No expression was observed for TIMP-1 or TIMP-2 in the embryo proper, trophoblasts, or the area of the uterine decidual reaction. Weak signals appeared for TIMP-1 only in the circular layer of myometrial smooth muscle and in some uterine stroma cells distant from the site of embryo implantation. The results suggest a central role for 92 kDa type IV collagenase and TIMP-3 in the extracellular proteolysis associated with implantation of the early embryo.
- Published
- 1995
30. Lack of type XVIII collagen results in anterior ocular defects
- Author
-
Naomi Fukai, Ritva Ylikärppä, Marko Määttä, Bjorn R. Olsen, Lauri Eklund, Raija Sormunen, Antti I. Kontiola, Aino Utriainen, and Taina Pihlajaniemi
- Subjects
Pathology ,medicine.medical_specialty ,Iris ,Type XVIII collagen ,Biology ,Eye ,Models, Biological ,Biochemistry ,Basement Membrane ,Mice ,Ciliary body ,Cornea ,Genetics ,medicine ,Collagen Type XVIII ,Animals ,Iris (anatomy) ,Pigment Epithelium of Eye ,Molecular Biology ,Intraocular Pressure ,Mice, Knockout ,Basement membrane ,Ciliary Body ,Knobloch syndrome ,medicine.disease ,medicine.anatomical_structure ,Microscopy, Fluorescence ,Lens (anatomy) ,sense organs ,Biotechnology - Abstract
Mice lacking type XVIII collagen have defects in the posterior part of the eye, including delayed regression of the hyaloid vasculature and poor outgrowth of the retinal vessels. We report here that these mice also have a fragile iris and develop atrophy of the ciliary body. The irises of Col18a1-/- mice can be seen to adhere to the lens and cornea. After the pupils begin to function, the double layer of epithelial cells separates at the apical cell contacts, leading to defoliation of its posterior pigment epithelial cell layer, and extracellular material begins to accumulate in the basement membrane zones of the iris. In contrast to the iris epithelia, where no clear signs of cellular atrophy were detected, the lack of type XVIII collagen resulted in atrophy of the pigmented epithelial cells of the ciliary body, and there were also ultrastructural abnormalities in the basement membrane zones. These changes did not lead to chronically elevated intraocular pressures, however. Our results indicate that type XVIII collagen is needed for the integrity of the epithelial basement membranes of the iris and the ciliary body and that its gene should therefore be taken into account as a new potential cause of anterior segment disorders in the eye.
- Published
- 2003
31. Vascular endothelial cells as a source of multipotent stem‐like cells
- Author
-
Bjorn R. Olsen
- Subjects
Endothelial stem cell ,Vasculogenesis ,Genetics ,Biology ,Molecular Biology ,Biochemistry ,Biotechnology ,Cell biology - Published
- 2012
32. Gene encoding a novel murine tissue inhibitor of metalloproteinases (TIMP), TIMP-3, is expressed in developing mouse epithelia, cartilage, and muscle, and is located on mouse chromosome 10
- Author
-
Masando Hayashi, Marie-Geneviève Mattei, Bjorn R. Olsen, Kimiko Hayashi, Suneel S. Apte, and Michael F. Seldin
- Subjects
Placenta ,Molecular Sequence Data ,Gene Expression ,In situ hybridization ,Matrix metalloproteinase ,Biology ,Muscle Development ,Chromosomes ,Epithelium ,Extracellular matrix ,Embryonic and Fetal Development ,Mice ,Gene expression ,medicine ,Animals ,Amino Acid Sequence ,Cloning, Molecular ,In Situ Hybridization ,Tissue Inhibitor of Metalloproteinase-3 ,Base Sequence ,Muscles ,Cartilage ,Chromosome Mapping ,Metalloendopeptidases ,Trophoblast ,Blotting, Northern ,Embryo, Mammalian ,Neoplasm Proteins ,Cell biology ,medicine.anatomical_structure ,Animals, Newborn ,Immunology ,Choroid plexus ,Developmental Biology - Abstract
Remodeling of the extracellular matrix (ECM) is an essential component of normal development and is also involved in the pathogenesis of arthritis and the spread of cancer. The matrix metalloproteinases and their natural inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), play an important role in this context. We have isolated mouse cDNA clones encoding a novel member of the TIMP family, designated TIMP-3. We have assigned the Timp-3 locus to the [C1-D1] region of mouse chromosome 10 using both genetic and cytogenetic methods. The conceptual translation product of the Timp-3 cDNA shows a high degree of similarity with ChIMP-3, a recently cloned chicken metalloproteinase inhibitor, as well as significant structural similarity with the amino acid sequences of the previously isolated members of this family, TIMP-1 and TIMP-2. The pattern of expression of Timp-3 in the developing mouse embryo is distinct from that previously reported for Timp-1. Timp-3 is expressed in cartilage and skeletal muscle, in myocardium, in the skin, oral and nasal epithelium, in the newborn mouse liver, in the epithelium of some tubular structures such as the developing bronchial tree, oesophagus, colon, urogenital sinus, bile duct, in the kidney, salivary glands, and in the choroid plexus of the brain. The patterns of Timp-3 expression in surface epithelia and in the epithelial lining of many tubular organs suggests that TIMP-3 may be involved in regulating ECM remodeling during the folding of epithelia and during the formation, branching, and expansion of epithelial tubes. In the mouse placenta, expression is seen in the trophoblast, raising the possibility that TIMP-3 may be involved in regulating trophoblastic invasion of the uterus. We propose a role for TIMP-3 in musculoskeletal and cardiac development, in the morphogenesis of certain epithelial structures, and placental implantation.
- Published
- 1994
33. Tissue-specific expression of type XII collagen during mouse embryonic development
- Author
-
Bjorn R. Olsen, Elizabeth D. Hay, C. May Griffith, and Suk P. Oh
- Subjects
Recombinant Fusion Proteins ,Immunocytochemistry ,Mice, Inbred Strains ,Cornea ,Tendons ,Mice ,Dermis ,Gene expression ,medicine ,Animals ,Cells, Cultured ,chemistry.chemical_classification ,Ligaments ,biology ,Fibroblasts ,Immunohistochemistry ,Molecular biology ,Blot ,Collagen, type I, alpha 1 ,medicine.anatomical_structure ,chemistry ,Polyclonal antibodies ,Immunology ,biology.protein ,Blood Vessels ,Collagen ,Glycoprotein ,Developmental Biology - Abstract
Polyclonal antibodies were raised in rabbits against a fusion peptide representing a portion of the amino-terminal non-triple-helical domain of mouse type XII collagen. The antibodies reacted with bands of 220 and 350 kDa on Western blots of mouse tissue extracts. Immunohistochemical analyses of mouse embryos demonstrated that type XII collagen is expressed mainly in dense connective tissues of tendons, ligaments, dermis, cornea, blood vessel walls, meninges, and developing membranous bones. Comparison of skin extracts and medium of cultured mouse skin fibroblasts by Western blotting showed that while tissue contain short 220 kDa type XII collagen polypeptides as well as the long form, cultured cells produce mainly the long form with 350 kDa polypeptides.
- Published
- 1993
34. Genomic organization and full-length cDNA sequence of human collagen X
- Author
-
Bjorn R. Olsen, Frank Beier, Wolf Bertling, Klaus von der Mark, Phyllis LuValle, and Ernst J Reichenberger
- Subjects
Evolution ,Sequence analysis ,Molecular Sequence Data ,Restriction Mapping ,Biophysics ,Regulatory Sequences, Nucleic Acid ,Biology ,Polymerase Chain Reaction ,Biochemistry ,Regulatory sequence ,Exon ,Rapid amplification of cDNA ends ,Structural Biology ,Sequence Homology, Nucleic Acid ,Complementary DNA ,Genetics ,Animals ,Amino Acid Sequence ,Molecular Biology ,Genomic organization ,Genomic Library ,Base Sequence ,Nucleic acid sequence ,Intron ,Promoter ,DNA ,Cell Biology ,Human cartilage ,Molecular biology ,Oligodeoxyribonucleotides ,Human type X ,Collagen ,Nucleotide sequence ,Chickens - Abstract
We have determined the full-length cDNA sequence of the human alpha 1(X) collagen gene by sequence analysis of a genomic clone ERG [(1991) Dev. Biol. 148, 562-572], and of cDNA fragments generated from a reverse transcribed as alpha 1(X) mRNA by PCR. We defined the promoter region, the transcription initiation site and the full-length 5'-untranslated region. We also report the exon/intron boundaries of the transcript and the complete 3'-untranslated region as well as a 3'-flanking sequence containing two additional polyadenylation signals. The promoter region is homologous to chicken and mouse type X promoters within several highly conserved regions. The genomic organization shows high homologies to chicken and mouse.
- Published
- 1992
35. An occipito‐temporal syndrome in adolescents with optimally controlled hyperphenylalaninaemia
- Author
-
Otto M. Henriksen, Peter B. Toft, J. Andresen, S. Wieslander, Hans C. Lou, Bjorn R. Olsen, F. Güttler, and I. Mikkelsen
- Subjects
Adult ,Pediatrics ,medicine.medical_specialty ,Pathology ,Adolescent ,Early adolescence ,Cerebral arteries ,Hyperphenylalaninemia ,Serum phenylalanine level ,Phenylketonurias ,Genetics ,Humans ,Medicine ,Genetics (clinical) ,medicine.diagnostic_test ,business.industry ,Neuropsychology ,Eeg abnormalities ,Electroencephalography ,Magnetic resonance imaging ,Syndrome ,medicine.disease ,Magnetic Resonance Imaging ,Temporal Lobe ,Phenotype ,Mutation ,Occipital Lobe ,business ,Dietary regimen - Abstract
The study included 16 adolescents with optimally controlled hyperphenylalaninaemia (McKusick 26160), of whom six did not require treatment according to conventional criteria. All except the two patients with lowest median serum phenylalanine level throughout childhood (most values at 200-300 mumol/L) had white matter abnormalities detectable with magnetic resonance imaging. The lesions were particularly prominent in the watershed regions between the posterior and middle cerebral arteries. In most patients with moderate or severe hyperphenylalaninaemia frontal white matter lesions were present as well. Normal proton magnetic resonance spectra indicated that the lesions were stable. Occipital EEG abnormalities were frequent, and deficient performance on a pattern-recognition test was a characteristic neuropsychological finding. Serum phenylalanine levels at about 300 mumol/L or below throughout childhood and early adolescence may be required to avoid lesions. The present study demonstrates the limitations of even an optimally controlled dietary regimen in hyperphenylalaninaemia.
- Published
- 1991
36. The complete primary structure of the human alpha1(VIII) chain and assignment of its gene (COL8A1) to chromosome 3
- Author
-
Y. Muragaki, Bjorn R. Olsen, Y Ninomiya, Marie-Geneviève Mattei, and Noriko Yamaguchi
- Subjects
Base Sequence ,Molecular Sequence Data ,Protein primary structure ,Nucleic acid sequence ,Chromosome Mapping ,Alpha (ethology) ,Biology ,Biochemistry ,Molecular biology ,Exon ,genomic DNA ,Chromosome 3 ,hemic and lymphatic diseases ,Homologous chromosome ,Humans ,Amino Acid Sequence ,Chromosomes, Human, Pair 3 ,Collagen ,Gene - Abstract
Type VIII collagen molecules, expressed by corneal and vascular endothelial cells, appear to be heterotrimers composed of two genetically distinct polypeptides, alpha 1 (VIII) and alpha 2(VIII), in the ratio of 2:1. Characterization of the rabbit alpha 1(VIII) gene has demonstrated that it consists of only four exons, one of which is large and encodes the entire triple-helical and carboxyl non-triple-helical domains. A similar exon organization has been found for the chicken alpha 1(X) and the mouse and human alpha 2(VIII) collagen genes. The genes encoding alpha 1(VIII), alpha 2(VIII), and alpha 1(X) collagen chains are therefore homologous members of a unique class of genes within the collagen superfamily. In the present paper we describe for the first time the primary structure of the human alpha 1(VIII) collagen chain, based on isolation and sequencing of a genomic DNA fragment. The results indicate that the human alpha 1(VIII) chain has the same domain structure as the rabbit protein. We also demonstrate that the gene is localized on the long arm of the human chromosome 3. The availability of genomic DNA encoding the human alpha 1(VIII) collagen chain and information about its chromosomal location should make it possible to examine whether hereditary diseases are linked to abnormalities in the structure or expression of the alpha 1(VIII) gene.
- Published
- 1991
37. The complete primary structure of two distinct forms of human alpha(IX) collagen chains
- Author
-
Y. Muragaki, Bjorn R. Olsen, Y Ninomiya, and Tomoatsu Kimura
- Subjects
chemistry.chemical_classification ,Protein subunit ,Protein primary structure ,Nucleic acid sequence ,Molecular cloning ,Biology ,Biochemistry ,Molecular biology ,Glycosaminoglycan ,chemistry ,Complementary DNA ,RNA splicing ,Glycoprotein - Abstract
Type IX collagen molecules contain three genetically distinct subunits. One of the subunits, alpha 2(IX), contains a covalently attached glycosaminoglycan side chain. A second subunit, alpha 1 (IX), has been found to be synthesized in two forms. The two forms are generated by the alternative use of two transcription start sites and splice patterns. The two forms have been found in chicken, mouse and human but cDNAs encoding both forms have only been reported for chicken. In the present report we describe the isolation of cDNA clones encoding the complete translated portion of both forms of human alpha 1(IX) collagen chains. Nucleotide sequence analysis has permitted the determination of the primary structure of both forms. These probes and sequences should prove useful in future studies of chondrodysplasias involving type IX collagen.
- Published
- 1990
38. Skeletal and Hematopoietic Defects in Mice Transgenic for Collagen Xa
- Author
-
Olena Jacenko, Bjorn R. Olsen, and S. Ito
- Subjects
Bone Development ,Tibia ,Bone development ,General Neuroscience ,Transgene ,Dwarfism ,Mice, Transgenic ,Regulatory Sequences, Nucleic Acid ,Biology ,Bone and Bones ,General Biochemistry, Genetics and Molecular Biology ,Hematopoiesis ,Cell biology ,Mice transgenic ,Collagen biosynthesis ,Mice ,Haematopoiesis ,History and Philosophy of Science ,Regulatory sequence ,Nucleic acid ,Animals ,Collagen ,Growth Plate ,Chickens - Published
- 1996
39. The highly conserved defender against the death 1 (DAD1) gene maps to human chromosome 14q11-q12 and mouse chromosome 14 and has plant and nematode homologs
- Author
-
Marie Geneviève Mattei, Bjorn R. Olsen, Suneel S. Apte, and Michael F. Seldin
- Subjects
Cell death ,Programmed cell death ,DAD1 ,Molecular Sequence Data ,Biophysics ,Xenopus ,Apoptosis ,Xenopus Proteins ,Biology ,Biochemistry ,Homology (biology) ,Mice ,Structural Biology ,Complementary DNA ,Genetics ,Homologous chromosome ,Animals ,Humans ,Amino Acid Sequence ,Molecular Biology ,Gene ,DNA Primers ,Chromosomes, Human, Pair 14 ,Base Sequence ,Sequence Homology, Amino Acid ,Gene map ,Chromosome Mapping ,Membrane Proteins ,Proteins ,Cell Biology ,Chromosome 14 ,biology.organism_classification ,Molecular biology ,Apoptosis Regulatory Proteins ,Sequence Alignment ,Chromosome 22 - Abstract
We have cloned the cDNA encoding the mouse DAD1 (defender against apoptotic cell death) protein. While showing an expected high homology with the previously cloned human and Xenopus DAD1-encoding cDNAs, this sequence has striking homology to partial cDNA sequences reported from O. sativa (rice) and C. elegans (nematode), suggesting the existence of plant and invertebrate homologs of this highly conserved gene. The human and mouse DAD1 genes map to chromosome 14q11–q12 and chromosome 14, respectively. This mapping data supports and extends the previously reported similarities between human chromosome 14q and mouse chromosome 14.
- Published
- 1995
40. Unchanged MRI of myelin in adolescents with PKU supplied with non-phe essential amino acids after dietary relaxation
- Author
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Hans C. Lou, J. Andresen, Flemming Güttler, Peter B. Toft, Bjorn R. Olsen, Per Guldberg, and Ingrid Mikkelsen
- Subjects
Male ,medicine.medical_specialty ,Adolescent ,Diet therapy ,Phenylalanine ,Myelin ,Phenylketonurias ,Internal medicine ,Humans ,Medicine ,Tyrosine ,Myelin Sheath ,chemistry.chemical_classification ,Relaxation (psychology) ,business.industry ,Tryptophan ,Brain ,General Medicine ,Magnetic Resonance Imaging ,Amino acid ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Pediatrics, Perinatology and Child Health ,Female ,Amino Acids, Essential ,business ,Myelin Proteins ,Follow-Up Studies - Published
- 1994
41. Shift in Spatial Pattern of Type X Collagen Expression in Embryonic Sterna Undergoing Endochondral Ossification Demonstrated by in Situ Hybridization and Immunohistochemistry
- Author
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Thomas F. Linsenmayer, Robert L. Trelstad, Bjorn R. Olsen, Ken-Ichi Iyama, Y Ninomiya, and Masando Hayashi
- Subjects
Pathology ,medicine.medical_specialty ,Sterna ,General Neuroscience ,In situ hybridization ,Biology ,biology.organism_classification ,Embryonic stem cell ,General Biochemistry, Genetics and Molecular Biology ,History and Philosophy of Science ,medicine ,Immunohistochemistry ,Endochondral ossification ,Type X collagen - Published
- 1990
42. Corrigendum
- Author
-
Masatoshi Jinnin, Bjorn R. Olsen, Tsuyoshi Ishihara, and Eileen Boye
- Subjects
Pathology ,medicine.medical_specialty ,business.industry ,Infantile hemangioma ,Medicine ,Dermatology ,General Medicine ,business - Published
- 2010
43. Cleidocranial Dysplasia in Mice
- Author
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L. F. Huang, Bjorn R. Olsen, Stefan Mundlos, and Paul B. Selby
- Subjects
Cleidocranial Dysplasia ,General Neuroscience ,Chromosome Mapping ,Mutagenesis (molecular biology technique) ,In situ hybridization ,Biology ,Embryo, Mammalian ,Clavicle ,Molecular biology ,Mice, Mutant Strains ,General Biochemistry, Genetics and Molecular Biology ,Mice ,medicine.anatomical_structure ,History and Philosophy of Science ,Mutagenesis ,Osteogenesis ,medicine ,Animals ,Humans ,Collagen ,Growth Plate ,In Situ Hybridization - Published
- 1996
44. Immortalization of chondrocytes from normal and mutant mice provides a tool to analyze cartilage matrix structure and differentiation
- Author
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Alan J. Grodzinsky, Frederic Bard, Florence Ruggiero, Bjorn R. Olsen, Frédéric Mallein-Gerin, Michel van der Rest, and Thomas M. Quinn
- Subjects
Mutant ,Cell Biology ,General Medicine ,Bone matrix ,Anatomy ,Biology ,Cell biology - Published
- 1995
45. Antibodies to Chick-Tendon Procollagen. Affinity Purification with the Isolated Disulfide-Linked NH2-Terminal Extensions and Reactivity with a Component in Embryonic Serum
- Author
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Darwin J. Prockop, Peter Dehm, and Bjorn R. Olsen
- Subjects
Immunodiffusion ,Macromolecular Substances ,Protein Conformation ,Radioimmunoassay ,Connective tissue ,Peptide ,Chick Embryo ,macromolecular substances ,Biochemistry ,Antibodies ,Antigen-Antibody Reactions ,Tendons ,Epitopes ,Antigen ,medicine ,Animals ,Chemical Precipitation ,Chymotrypsin ,Trypsin ,Carbon Radioisotopes ,Disulfides ,Amines ,Protein Precursors ,Antiserum ,chemistry.chemical_classification ,integumentary system ,biology ,Chemistry ,Molecular biology ,Peptide Fragments ,Procollagen peptidase ,Microbial Collagenase ,medicine.anatomical_structure ,Chromatography, Gel ,Collagenase ,biology.protein ,Electrophoresis, Polyacrylamide Gel ,Collagen ,Rabbits ,Antibody ,Cysteine ,medicine.drug - Abstract
Antisera were prepared by immunizing a rabbit with procollagen synthesized and secreted by cells from chick embryo tendons. Specific antibodies were then purified from the antisera by using an immunoadsorbent which contained the isolated NHz-terminal extensions of procollagen. The purified antibodies were shown to react specifically with intact procollagen as well as with procollagen in which the interchain disulfide bonds were ruptured by reduction under non-denaturing conditions. The antibodies also reacted with the pro-a1 chain but not the pro-a2 chain isolated from the procollagen. There was no reaction after the intrachain bonds in the pro-a chains of the procollagen were reduced under denaturing conditions and alkylated. In the course of characterizing the antibodies it was shown that the NH2-terminal extensions on the two pro-a1 chains and the one pro-a2 chain of type I procollagen are non-identical. Also, it was shown that the serum of chick embryos contains an antigen which reacts with the specific antibodies to procollagen. Collagen is synthesized by connective tissue cells in a precursor form called procollagen which is larger than the collagen molecule because of peptide extensions on the NH2-terminal end of each of the three a chains (for recent review, see [l]). The amino-acid composition of the extensions differs from that of collagen and it includes cysteine and tryptophan, aminoacids which are not found in collagen itself. A large fraction of the procollagen synthesized and secreted by cells from chick embryo tendons has been shown to consist of pro-a chains linked by interchain disulfide bonds [2]. Interchain disulfide bonds have also been demonstrated in procollagens from cultured fibroblasts [3,4], membranous bone [5,6], and lens cells from chick embryos [7]. Antibodies against the NH2-terminals extensions of procollagen have recently been prepared by using procollagen from three different sources for immunization. Purified antibodies to the NH2-terminal extension of procollagen which was extracted from the skin of cattle with the disease called dermatosparaxis were shqwn to react both with the native procollagen from the skin of the diseased cattle and with the isolated polypeptide chains from this form of procollagen [S]. Enzymes. Collagenase or clostridiopeptidase A (EC
- Published
- 1974
46. Medullary carcinoma of the thyroid.Diagnostic problems
- Author
-
I. O. Brennhovd, K. M. Gautvik, Bjorn R. Olsen, Trine Normann, and J. V. Johannessen
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Stromal cell ,business.industry ,Thyroid ,medicine.disease ,Thyroid carcinoma ,medicine.anatomical_structure ,Oncology ,Medullary carcinoma ,Calcitonin ,medicine ,business ,Thyroid tumors - Abstract
Light microscopy is usually considered sufficient for the diagnosis of medullary carcinoma of the thyroid (MCT). As stromal amyloid is not always present and the tumor may exhibit great variation in growth pattern, light microscopy alone, however, may lead to misinterpretations. Of 1670 thyroid carcinomas registered durging a 15-year period in Norway, 42 were originally interpreted as MCT. The slides were reviewed and the diagnosis maintained in 33 cases only. Twenty-four additional cases were found by reviewing histopathologic slides from neoplasms originally registered as other types of thyroid tumors. Of 57 cases of MCT, stromal amyloid was demonstrated in 43. Calcitonin measurements and electron microscopy, even on formalin-fixed material, were valuable aids in establishing the correct diagnosis, though none of these methods are unequivocal. Different aspects of the problems concerning the diagnosis of MCT are discussed through the detailed presentation of five patients.
- Published
- 1976
47. Characterization of the Amino-Terminal Segment in Type III Procollagen
- Author
-
Bjorn R. Olsen, Rupert Timpl, and Hans Nowack
- Subjects
Erythrocytes ,Protein Conformation ,Stereochemistry ,Radioimmunoassay ,Peptide ,macromolecular substances ,Biochemistry ,chemistry.chemical_compound ,Fetus ,Protein structure ,medicine ,Animals ,Amino Acid Sequence ,Disulfides ,Amino Acids ,Peptide sequence ,Skin ,chemistry.chemical_classification ,Binding Sites ,Molecular mass ,Hemagglutination Tests ,Amino acid ,Molecular Weight ,Procollagen peptidase ,Microbial Collagenase ,chemistry ,Collagenase ,Cattle ,Cyanogen bromide ,Collagen ,Procollagen ,Protein Binding ,medicine.drug - Abstract
Native type III collagen and procollagen were prepared from fetal bovine skin. Examination of the cleavage products produced by digestion with tadpole collagenase demonstrated that the three palpha1(III) chains of type III procollagen were linked together by disulfide bonds occurring at both the amino-terminal and carboxy-terminal portions of the molecule. Type III collagen contained interchain disulfide bonds only in the carboxy-terminal region of the molecule. After digestion of procollagen with bacterial collagenase an amino-terminal, triple-stranded peptide fragment was isolated. The reduced and alkylated chain constituents of this fragment had molecular weights of about 21 000. After digestion of procollagen with cyanogen bromide a related triple-stranded fragment was isolated. The chains of the cyanogen bromide fragment had a molecular weight of about 27 000. When the collagenase-derived peptide was fully reduced and alkylated, it became susceptible to further digestion with bacterial collagenase. This treatment released a fragment of about 97 amino acid residues which contained 12 cystein residues and had an amino acid composition typical for globular proteins. A second, non-helical fragment of about 48 amino acid residues contained three cysteines. This latter fragment is formed from sequences that overlap the amino-terminal region in the collagen alpha1(III) chain by 20 amino acids and possesses an antigenic determinant specific for the alpha1(III) chain. The collagenase-sensitive region exposed by reduction comprised about 33 amino acid residues. It was recovered as a mixture of small peptides. These results indicate that the amino-terminal region of type III procollagen has the same type of structure as the homologous region of type I procollagen. It consists of a globular, a collagen-like and a non-helical domain. Interchain disulfide bonding and the occurrence of cysteines in the non-helical domain are, however, unique for type III procollagen.
- Published
- 1976
48. Diacetyl (Acetoin) Reductase from Aerobacter aerogenes. Structural Properties
- Author
-
Terje B. Christensen, Fredrik C. Størmer, Bjorn R. Olsen, and Øyvind Hetland
- Subjects
Acetoin reductase ,Chemical Phenomena ,Chemistry ,Enterobacter ,Electrophoresis, Disc ,Biochemistry ,Diacetyl ,Aerobacter aerogenes ,Molecular Weight ,Alcohol Oxidoreductases ,Microscopy, Electron ,chemistry.chemical_compound - Published
- 1971
49. Structure of Protocollagen Proline Hydroxylase from Chick Embryos
- Author
-
Kari I. Kivirikko, Darwin J. Prockop, Bjorn R. Olsen, and Richard A. Berg
- Subjects
Macromolecular Substances ,Stereochemistry ,Procollagen-Proline Dioxygenase ,Chick Embryo ,Models, Biological ,Biochemistry ,Chromatography, Affinity ,Mixed Function Oxygenases ,law.invention ,chemistry.chemical_compound ,Protein structure ,Tetramer ,law ,Animals ,Scattering, Radiation ,Protein Precursors ,Probability ,chemistry.chemical_classification ,Chick embryos ,Hydroxyproline ,Microscopy, Electron ,Crystallography ,Protocollagen Proline Hydroxylase ,Enzyme ,Monomer ,chemistry ,Electrophoresis, Polyacrylamide Gel ,Collagen ,Electron microscope - Abstract
Protocollagen proline hydroxylase was purified from chick embryos with an affinity-column procedure which yielded pure enzyme in a tetramer form. Electron microscopy of the enzyme after it was largely dissociated into monomers indicated that the monomers were rod-shaped with a diameter of 3.31 ± 0.07 nm (S.E.M.) and a length of 6.95 ± 0.07 nm. In preparations of the enzyme in which the protein was partially dissociated, dumb-bell and V-shaped structures were seen which morphologically consisted of two sub-structures each with dimensions similar to those of the isolated monomers. The results suggested that these structures were dimers in which the monomers were joined at one end with an angle between their longitudinal axes. The largest regular protein structures seen in preparations of the enzyme were about 8 × 8 nm and in some of these structures four sub-structures were seen, indicating that they were tetramers. On the basis of the data presented here we propose a model of the tetramer in which two V-shaped dimers were interlocked. Further studies demonstrated that the single-ring and four-ring structures seen by electron microscopy of enzyme preparations obtained by a previous purification procedure were not the enzyme.
- Published
- 1973
50. A conformational model of serine transfer RNA proposed on the basis of electron microscopy
- Author
-
L.O. Frøholm and Bjorn R. Olsen
- Subjects
Basis (linear algebra) ,Chemistry ,Cryo-electron microscopy ,Biophysics ,Cell Biology ,Biochemistry ,law.invention ,Serine ,Crystallography ,Structural Biology ,law ,Transfer RNA ,Genetics ,Electron microscope ,Molecular Biology - Published
- 1969
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