Resistance of small leucine-rich repeat proteoglycans to proteolytic degradation during interleukin-1-stimulated cartilage catabolism

A bovine nasal-cartilage culture system has been utilized to analyse the ca tabolic events occurring in response to interleukin-1 beta Over a 14-day pe riod. An early event following the start of interleukin-l treatment was the release of glycosaminoglycan into the culture medium. This release was acc ompanied by the appearance in the tissue, and shortly thereafter also in th e culture media, of a globular domain (G1)-containing aggrecan degradation product generated by the action of aggrecanase. Link protein was also relea sed from the cartilage with a similar timeframe to that of the G1 fragment, although there was no evidence of its proteolytic degradation. By comparis on with aggrecan, the small leucine-rich repeat proteoglycans decorin, bigl ycan and lumican showed a resistance to both proteolytic cleavage and relea se throughout the culture period. In contrast, fibromodulin exhibited a mar ked decrease in size after day 4, presumably due to proteolytic modificatio n, but the major degradation product was retained throughout the culture pe riod. Also in contrast with the early changes in the components of the prot eoglycan aggregate, type II collagen did not display signs of extensive deg radation until much later in the culture period. Collagen degradation produ cts compatible with collagenase action first appeared in the medium by day 10 and increased thereafter. These data demonstrate that the leucine-rich r epeat proteoglycans are resistant to proteolytic action during interleukin- l-stimulated cartilage catabolism, compared with aggrecan. This resistance and continued interaction with the surface of the collagen fibrils may help to stabilize the collagen fibrillar network and protect it from extensive proteolytic attack during the early phases of cartilage degeneration.