A major and early feature of cartilage degeneration is
proteoglycan breakdown. Matrix
metalloprotease (MMP)-13 plays an important role in cartilage degradation in
osteoarthritis (OA). This
MMP, in addition to initiating
collagen fibre cleavage, acts on several
proteoglycans. One of the
proteoglycan families, termed
small leucine-rich proteoglycans (SLRPs), was found to be involved in
collagen fibril formation/interaction, with some members playing a role in the OA process. We investigated the ability of MMP-13 to cleave members of two classes of SLRPs:
biglycan and
decorin; and
fibromodulin and
lumican. SLRPs were isolated from human normal and OA cartilage using
guanidinium chloride (4 mol/l) extraction. Digestion products were examined using Western blotting. The identities of the MMP-13 degradation products of
biglycan and
decorin (using specific substrates) were determined following electrophoresis and microsequencing. We found that the SLRPs studied were cleaved to differing extents by human MMP-13. Although only minimal cleavage of
decorin and
lumican was observed, cleavage of
fibromodulin and
biglycan was extensive, suggesting that both molecules are preferential substrates. In contrast to
biglycan,
decorin and
lumican, which yielded a degradation pattern similar for both normal and OA cartilage,
fibromodulin had a higher level of degradation with increased cartilage damage. Microsequencing revealed a novel major cleavage site (... G177/V178) for
biglycan and a potential cleavage site for
decorin upon exposure to MMP-13. We showed, for the first time, that MMP-13 can degrade members from two classes of the SLRP family, and identified the site at which
biglycan is cleaved by MMP-13. MMP-13 induced SLRP degradation may represent an early critical event, which may in turn affect the
collagen network by exposing the MMP-13 cleavage site in this macromolecule. Awareness of SLRP degradation products, especially those of
biglycan and
fibromodulin, may assist in early detection of OA cartilage degradation.