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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11 January 1999
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January 11 1999
Role of CDMP-1 in Skeletal Morphogenesis: Promotion of Mesenchymal Cell Recruitment and Chondrocyte Differentiation
Noriyuki Tsumaki,
Noriyuki Tsumaki
*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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Kazuhiro Tanaka,
Kazuhiro Tanaka
*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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Eri Arikawa-Hirasawa,
Eri Arikawa-Hirasawa
*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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Takanobu Nakase,
Takanobu Nakase
*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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Tomoatsu Kimura,
Tomoatsu Kimura
*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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J. Terrig Thomas,
J. Terrig Thomas
*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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Takahiro Ochi,
Takahiro Ochi
*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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Frank P. Luyten,
Frank P. Luyten
*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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Yoshihiko Yamada
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
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Noriyuki Tsumaki
*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
Kazuhiro Tanaka
*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
Eri Arikawa-Hirasawa
*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
Takanobu Nakase
*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
Tomoatsu Kimura
*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
J. Terrig Thomas
*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
Takahiro Ochi
*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
Frank P. Luyten
*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
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
Address correspondence to Yoshihiko Yamada, Ph.D., Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 9000 Rockville Pike, Building 30, Room 405, Bethesda, MD 20892. Tel.: (301) 496-2111. Fax: (301) 402-0897. E-mail: [email protected]
Frank P. Luyten's present address is Division of Rheumatology, Universitaire Ziekenhuizen Leuven, U.Z. Pellenberg, Weligerveld 1, 3212 Lubbeek (Pellenberg), Belgium.
Received:
March 20 1998
Revision Received:
November 18 1998
Online ISSN: 1540-8140
Print ISSN: 0021-9525
1999
J Cell Biol (1999) 144 (1): 161–173.
Article history
Received:
March 20 1998
Revision Received:
November 18 1998
Citation
Noriyuki Tsumaki, Kazuhiro Tanaka, Eri Arikawa-Hirasawa, Takanobu Nakase, Tomoatsu Kimura, J. Terrig Thomas, Takahiro Ochi, Frank P. Luyten, Yoshihiko Yamada; Role of CDMP-1 in Skeletal Morphogenesis: Promotion of Mesenchymal Cell Recruitment and Chondrocyte Differentiation . J Cell Biol 11 January 1999; 144 (1): 161–173. doi: https://doi.org/10.1083/jcb.144.1.161
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