title: A role for the BMP antagonist chordin in endochondral ossification.
abstract: 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.
authors.affiliation: Department of Orthopedics, School of Medicine and Dentistry, University of Rochester, New York, USA.
authors.forename: Donghui
authors.initials: D
authors.lastname: Zhang
authors.forename: Cristin M
authors.initials: CM
authors.lastname: Ferguson
authors.forename: Regis J
authors.initials: RJ
authors.lastname: O'Keefe
authors.forename: J Edward
authors.initials: JE
authors.lastname: Puzas
authors.forename: Randy N
authors.initials: RN
authors.lastname: Rosier
authors.forename: Paul R
authors.initials: PR
authors.lastname: Reynolds
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002356:Cartilage / Q000196:embryology* / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D002642:Chick Embryo; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D024081:Collagen Type IX / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D018878:Limb Buds; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D010012:Osteogenesis
chemical_list: D019485:Bone Morphogenetic Proteins; D024081:Collagen Type IX; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C054234:chordin