ABNORMAL COMPARTMENTALIZATION OF CARTILAGE MATRIX COMPONENTS IN MICE LACKING COLLAGEN-X - IMPLICATIONS FOR FUNCTION

There are conflicting views on whether collagen X is a purely structur al molecule, or regulates bone mineralization during endochondral ossi fication. Mutations in the human collagen alpha 1(X) gene (COL10A1) in Schmid metaphyseal chondrodysplasia (SMCD) suggest a supportive role. But mouse collagen alpha 1(X) gene (Col10a1) null mutants were previo usly reported to show no obvious phenotypic change, We have generated collagen X deficient mice, which shows that deficiency does have pheno typic consequences which partly resemble SMCD, such as abnormal trabec ular bone architecture, In particular, the mutant mice develop coxa va ra, a phenotypic change common in human SMCD. Other consequences of th e 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 co llagen X plays a role in the normal distribution of matrix vesicles an d proteoglycans within the growth plate matrix. Collagen X deficiency impacts on the supporting properties of the growth plate and the miner alization process, resulting in abnormal trabecular bone. This hypothe sis would accommodate the previously conflicting views of the function of collagen X and of the molecular pathogenesis of SMCD.