A Role for the BMP Antagonist Chordin in Endochondral Ossification

• Published in: Journal of bone and mineral research Vol. 17; no. 2; pp. 293 - 300
• Main Authors: Zhang, Donghui, Ferguson, Cristin M., O'Keefe, Regis J., Puzas, J. Edward, Rosier, Randy N., Reynolds, Paul R.
• Format: Journal Article
• Language: English
• Published: Washington, DC John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR) 01.02.2002; American Society for Bone and Mineral Research
• Subjects: Animals; Biological and medical sciences; bone morphogenetic proteins; Bone Morphogenetic Proteins - metabolism; Cartilage - embryology; Cartilage - physiology; Cell Differentiation; Cells, Cultured; Chick Embryo; chondrocyte differentiation; Chondrocytes - cytology; Chondrocytes - metabolism; chordin; Chordin protein; Collagen Type IX - genetics; Embryology: invertebrates and vertebrates. Teratology; endochondral ossification; Experimental organogenesis; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Glycoproteins - genetics; Glycoproteins - metabolism; Intercellular Signaling Peptides and Proteins; Limb Buds; limb growth; Organogenesis. Physiological fonctions; Osteoblasts - cytology; Osteoblasts - physiology; Osteogenesis; Embryonic development; Embryo; Chondrocyte; Growth; Gene expression; Osteoarticular system; Vertebrata; Epiphyseal cartilage; Bone morphogenetic protein; Animal; Limb; Chicken; Antagonist; Aves; Differentiation
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1359/jbmr.2002.17.2.293

Bone morphogenetic proteins (BMPs) are ubiquitous regulators of cellular growth and differentiation. A variety of processes modulate BMP activity, including negative regulation by several distinct binding proteins. One such BMP antagonist chordin has a role in axis determination and neural induction in the early embryo. In this study, a role for chordin during endochondral ossification has been investigated. During limb development, Chordin expression was detected only at the distal ends of the skeletal elements. In cultured embryonic sternal chondrocytes, Chordin expression was related inversely to the stages of maturation. Further, treating cultured chondrocytes with chordin interfered with maturation induced by treatment with BMP‐2. These results suggest that chordin may negatively regulate chondrocyte maturation and limb growth in vivo. To address this hypothesis, chordin protein was expressed ectopically in Hamburger‐Hamilton (HH) stage 25‐27 embryonic chick limbs. The phenotypic changes and alteration of gene expression in treated limbs revealed that overexpression of chordin protein delayed chondrocyte maturation in developing skeletal elements. In summary, these findings strongly support a role for chordin as a negative regulator of endochondral ossification.