The long-term goal of these studies is to understand the regulated assembly, structure, and functional roles of cartilage extracellular matrix components during development. To reach this goal, we will use a combination of DNA cloning, immunohistochemistry, and transgenic mice technology to analyze the expression and function of the short-chain collagen X in hypertrophic cartilage, and of the FACIT components IX and XII in cartilage development. The cloned mouse genes for these collagens will be used to make vectors for gene targeting by homologous recombination in embryonic stem cells, as well as constructs designed to produce dominant negative suppressor mutations in mice. Analysis of mice with such engineered defects will provide novel and important information about the role of collagen components in cartilage structure and development as well as provide animal, models for cartilage abnormalities in man. Finally, we will use a sensitive subtractive hybridization technique to clone cDNAs encoding factors involved in the transition from small chondrocytes to hypertrophic chondrocytes in maturing cartilage. This will provide the initial entry point for a detailed molecular understanding of how the transition between the two chondrocyte states is regulated, and thus a basis for examining the molecular defects in many chondrodysplasias.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Method to Extend Research in Time (MERIT) Award (R37)
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Harvard University
Anatomy/Cell Biology
Schools of Medicine
United States
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Hu, Kai; Olsen, Bjorn R; Besschetnova, Tatiana Y (2017) Cell autonomous ANTXR1-mediated regulation of extracellular matrix components in primary fibroblasts. Matrix Biol 62:105-114
Nagao, Masashi; Hamilton, John L; Kc, Ranjan et al. (2017) Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis. Sci Rep 7:13027
Hu, Kai; Olsen, Bjorn R (2017) Vascular endothelial growth factor control mechanisms in skeletal growth and repair. Dev Dyn 246:227-234
Olsen, Bjorn R; Berendsen, Agnes D; Besschetnova, Tatiana Y et al. (2016) Fell-Muir Lecture: Regulatory mechanisms of skeletal and connective tissue development and homeostasis - lessons from studies of human disorders. Int J Exp Pathol 97:296-302
Hu, Kai; Olsen, Bjorn R (2016) The roles of vascular endothelial growth factor in bone repair and regeneration. Bone 91:30-8
Huang, Wei; Li, Qing; Amiry-Moghaddam, Mahmood et al. (2016) Critical Endothelial Regulation by LRP5 during Retinal Vascular Development. PLoS One 11:e0152833
Duan, Xuchen; Bradbury, Seth R; Olsen, Bjorn R et al. (2016) VEGF stimulates intramembranous bone formation during craniofacial skeletal development. Matrix Biol 52-54:127-140
Nagao, M; Cheong, C W; Olsen, B R (2016) Col2-Cre and tamoxifen-inducible Col2-CreER target different cell populations in the knee joint. Osteoarthritis Cartilage 24:188-91
Hu, Kai; Olsen, Bjorn R (2016) Osteoblast-derived VEGF regulates osteoblast differentiation and bone formation during bone repair. J Clin Invest 126:509-26
Huang, Wei; Olsen, Bjorn R (2015) Skeletal defects in Osterix-Cre transgenic mice. Transgenic Res 24:167-72

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