Role of CDMP-1 in skeletal morphogenesis: promotion of mesenchymal cell recruitment and chondrocyte differentiation.
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.
Tsumaki
N
N
Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Tanaka
K
K
Arikawa-Hirasawa
E
E
Nakase
T
T
Kimura
T
T
Thomas
J T
JT
Ochi
T
T
Luyten
F P
FP
Yamada
Y
Y
D000818:Animals; D019485:Bone Morphogenetic Proteins; D001842:Bone and Bones / Q000196:embryology*; D002356:Cartilage / Q000196:embryology / Q000378:metabolism; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology*; D015870:Gene Expression; D055428:Growth Differentiation Factor 5; D006133:Growth Substances / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D013234:Stem Cells
D019485:Bone Morphogenetic Proteins; D055428:Growth Differentiation Factor 5; D006133:Growth Substances