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© The Rockefeller University Press, 0021-9525/1999//161 $5.00
The Journal of Cell Biology, Volume 144, Number 1, , 1999 161-173

Articles

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



Noriyuki Tsumaki*,{ddagger}, Kazuhiro Tanaka*, Eri Arikawa-Hirasawa*, Takanobu Nakase{ddagger}, Tomoatsu Kimura§, J. Terrig Thomas||, Takahiro Ochi{ddagger}, 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; {ddagger} 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.

Key Words: bone morphogenetic protein family • cartilage • ectopic expression • skeletal abnormalities • transgenic mice

Abbreviations used in this paper: AgNOR, silver stain for nucleolar organizer regions; BMP, bone morphogenetic protein; CDMP-1, cartilage-derived morphogenetic protein-1; d.p.c., days postcoitus; GDF5, growth and differentiation factor 5.

Frank P. Luyten's present address is Division of Rheumatology, Universitaire Ziekenhuizen Leuven, U.Z. Pellenberg, Weligerveld 1, 3212 Lubbeek (Pellenberg), Belgium.


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