Abnormal Compartmentalization of Cartilage Matrix Components in Mice Lacking Collagen X: Implications for Function |
| |
| Authors: | 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 Kathryn S.E. Cheah |
| |
| Affiliation: | *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 |
| |
| Abstract: | 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 α1(X) gene (COL10A1) in Schmid metaphyseal chondrodysplasia (SMCD) suggest a supportive role. But mouse collagen α1(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. |
| |
| Keywords: | |
|
|
