Differences in Chain Usage and Cross-linking Specificities of Cartilage Type V/XI Collagen Isoforms with Age and Tissue

Collagen type V/XI is a minor but essential component of collagen fibrils in vertebrates. We here report on age-and tissue-related variations in isoform usage in cartilages. With maturation of articular cartilage, the alpha 1(V) chain progressively replaced the alpha 2(XI) chain. A mix of the molecular isoforms, alpha 1(XI) alpha 1(V) alpha 3(XI) and alpha 1(XI) alpha 2(XI) alpha 3(XI), best explained this finding. A prominence of alpha 1(V) chains is therefore characteristic and a potential biomarker of mature mammalian articular cartilage. Analysis of cross-linked peptides showed that the alpha 1(V) chains were primarily cross-linked to alpha 1(XI) chains in the tissue and hence an integral component of the V/XI polymer. From nucleus pulposus of the intervertebral disc (in which the bulk collagen monomer is type II as in articular cartilage), type V/XI collagen consisted of a mix of five genetically distinct chains, alpha 1(XI), alpha 2(XI), alpha 3(XI), alpha 1(V), and alpha 2(V). These presumably were derived from several different molecular isoforms, including alpha 1(XI) alpha 2(XI) alpha 3(XI), (alpha 1(XI))(2) alpha 2(V), and others. Meniscal fibrocartilage shows yet another V/XI phenotype. The findings support and extend the concept that the clade B subfamily of COL5 and COL11 gene products should be considered members of the same collagen subfamily, from which, in combination with clade A gene products (COL2A1 or COL5A2), a range of molecular isoforms has evolved into tissue-dependent usage. We propose an evolving role for collagen V/XI isoforms as an adaptable polymeric template of fibril macro-architecture.