J. Cell Biol.
© The Rockefeller University Press
0021-9525/97/01/459/13 $2.00
Volume 136, Number 2, January 27, 1997 459-471

Abnormal Compartmentalization of Cartilage Matrix Components in Mice Lacking Collagen X: Implications for Function

Kin Ming Kwan,^* Michael K.M. Pang, Sheila Zhou,^§ Soot Keng Cowan,^* Richard Y.C. Kong,^* Tim Pfordte, Bjorn R. Olsen, David O. Sillence,^¶ Patrick P.L. Tam,^§ and Kathryn S.E. Cheah^*

^* Biochemistry Department and  Oral Biology Unit, The University of Hong Kong, Hong Hong; ^§ Children's Medical Research Institute, Wentworthville, N.S.W. 2145, Australia, and  Department of Cell Biology, Harvard University, Boston, MA; and ^¶ Department of Clinical Genetics, New Children's Hospital, Westmead, NSW 2145, Australia

There are conflicting views on whether collagen X is a purely structural molecule, or regulates bone mineralization during endochondral ossification. Mutations in the human collagen 1(X) gene (COL10A1) in Schmid metaphyseal chondrodysplasia (SMCD) suggest a supportive role. But mouse collagen 1(X) gene (Col10a1) null mutants were previously reported to show no obvious phenotypic change. We have generated collagen X deficient mice, which shows that deficiency does have phenotypic consequences which partly resemble SMCD, such as abnormal trabecular bone architecture. In particular, the mutant mice develop coxa vara, a phenotypic change common in human SMCD. Other consequences of the mutation are reduction in thickness of growth plate resting zone and articular cartilage, altered bone content, and atypical distribution of matrix components within growth plate cartilage. We propose that collagen X plays a role in the normal distribution of matrix vesicles and proteoglycans within the growth plate matrix. Collagen X deficiency impacts on the supporting properties of the growth plate and the mineralization process, resulting in abnormal trabecular bone. This hypothesis would accommodate the previously conflicting views of the function of collagen X and of the molecular pathogenesis of SMCD.

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