Collagens and cartilage matrix homeostasis

At least 27 types of collagen, the products of forty genes, are expressed in the tissues of higher vertebrates. Cartilage has a distinctive collagen phenotype. Two-thirds of the dry weight of adult articular cartilage is collagen. Proteolysis of this collagen framework is integral to the process of cartilage destruction and joint failure in osteoarthritis. Molecular studies are revealing the mechanisms of assembly of cartilage collagen fibrils. The nascent Type 11 collagen fibril is a heteropolymer, with collagen IX molecules covalently linked to the surface and collagen XI forming a filamentous template at the core, which regulates fibril diameter through its retained N-propeptide domains. This structure presents a challenge to understanding how fibril growth and collagen network maturation are brought about. Proteolytic remodeling, other than that mediated by collagenases, would appear to be involved, but the proteases and molecular mechanisms are still undefined. Valuable insights and predictions on the function of the individual collagen types in cartilage continue to come from the study of skeletal dysplasia syndromes caused by mutations in genes for collagens and associated matrix proteins.