J. Cell Biol., Volume 144, Number 1, January 11, 1999 161-173

Role of CDMP-1 in Skeletal Morphogenesis: Promotion of Mesenchymal Cell Recruitment and Chondrocyte Differentiation

Noriyuki Tsumaki,^* Kazuhiro Tanaka,^* Eri Arikawa-Hirasawa,^* Takanobu Nakase, Tomoatsu Kimura,^§ J. Terrig Thomas, Takahiro Ochi, Frank P. Luyten, and Yoshihiko Yamada^*

^* 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

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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