Role of CDMP-1 in Skeletal Morphogenesis: Promotion of Mesenchymal Cell Recruitment and Chondrocyte Differentiation |
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| Authors: | Noriyuki Tsumaki Kazuhiro Tanaka Eri Arikawa-Hirasawa Takanobu Nakase Tomoatsu Kimura J. Terrig Thomas Takahiro Ochi Frank P. Luyten Yoshihiko Yamada |
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| Affiliation: | *Craniofacial Developmental Biology and Regeneration Branch, ‖Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892; ‡Department of Orthopaedic Surgery, Osaka University Medical School, Suita 565-0871, Japan; and §Department of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan |
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| Abstract: | Cartilage provides the template for endochondral ossification and is crucial for determining the length and width of the skeleton. Transgenic mice with targeted expression of recombinant cartilage-derived morphogenetic protein-1 (CDMP-1), a member of the bone morphogenetic protein family, were created to investigate the role of CDMP-1 in skeletal formation. The mice exhibited chondrodysplasia with expanded cartilage, which consists of the enlarged hypertrophic zone and the reduced proliferating chondrocyte zone. Histologically, CDMP-1 increased the number of chondroprogenitor cells and accelerated chondrocyte differentiation to hypertrophy. Expression of CDMP-1 in the notochord inhibited vertebral body formation by blocking migration of sclerotome cells to the notochord. These results indicate that CDMP-1 antagonizes the ventralization signals from the notochord. Our study suggests a molecular mechanism by which CDMP-1 regulates the formation, growth, and differentiation of the skeletal elements. |
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| Keywords: | bone morphogenetic protein family cartilage ectopic expression skeletal abnormalities transgenic mice |
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