Modulating chondrocyte hypertrophy in growth plate and osteoarthritic cartilage.

induce expression of active proteinases leading to increased matrix degradation. Other fragments increase matrix synthesis and cellular proliferation. Several studies have suggested that type II collagen fragments might influence chondrocyte differentiation in endochondral ossification, and we hypothesise that collagen II fragments might also promote cellular hypertrophy when they are over-produced in OA. Collagen II fragments have been of interest to researchers investigating arthritic disease for some time. Initially they were studied for their utility as biomarkers to monitor collagen synthesis and degradation. Assays for the collagen II Nand C-propeptides have been developed as markers of collagen biosynthesis, whereas assays for peptides derived from the telopeptide and triple helical regions are in development as markers of degradation. More recently, in vitro studies have suggested that collagen II fragments might exacerbate osteoarthritis by stimulating induction and activation of matrix metalloproteinases which further degrade the collagen matrix and initiate a positive feedback loop. For example, stimulation of cartilage explants with collagen II fragments generated by bacterial collagenase (which cleaves a highly repetitive amino acid sequence in collagen triple helices) causes an increase in gelatinases MMP-2 and -9; once cleaved at the primary cleavage site by collagenases, collagen II is readily degraded by gelatinases. In other examples, stimulation of cartilage explants with collagen II fragments generated by cyanogen bromide, increases MMP-13 expression and collagen degradation. The cyanogen bromide peptides of collagen II also induce chondrocyte hypertrophy, type X collagen expression and apoptosis in vitro. Although none of these fragments are physiological in their origin, the results do suggest that type II collagen fragments might have a role in hypertrophy in endochondral ossification. More importantly, the results J Musculoskelet Neuronal Interact 2008; 8(4):308-310