Abnormal compartmentalization of cartilage matrix components in mice lacking collagen X: implications for function

J Cell Biol. 1997 Jan 27;136(2):459-71. doi: 10.1083/jcb.136.2.459.

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 alpha1 (X) gene (COL10A1) in Schmid metaphyseal chondrodysplasia (SMCD) suggest a supportive role. But mouse collagen alpha1 (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Matrix
  • Cartilage, Articular / chemistry
  • Cartilage, Articular / cytology
  • Collagen / deficiency
  • Collagen / genetics
  • Collagen / physiology*
  • Female
  • Femur
  • Gene Targeting
  • Growth Plate / chemistry
  • Growth Plate / cytology*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Osteochondrodysplasias / genetics
  • Osteochondrodysplasias / physiopathology
  • Osteogenesis*
  • Proteoglycans / analysis*

Substances

  • Proteoglycans
  • Collagen