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

TLDR

Collagen X’s role in endochondral ossification is debated, with human COL10A1 mutations indicating a supportive function while mouse null mutants were initially reported to show no phenotype. The authors hypothesize that collagen X regulates the normal distribution of matrix vesicles and proteoglycans in the growth plate, reconciling conflicting views and explaining SMCD pathogenesis. Collagen X deficiency in mice causes abnormal trabecular bone, coxa vara, reduced growth plate resting zone thickness, altered cartilage composition, and mislocalized matrix components, mirroring SMCD phenotypes and indicating impaired growth plate support and mineralization.

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.