Usurped SLRPs: novel arthritis biomarkers exposed by catabolism of small leucine-rich proteoglycans?

Proficient operativity of articular cartilage is effectively maintained via the specialized qualities of multiple macro-molecular components, including a notable array of collagens and proteoglycans. Critical attributes of collagen organization and cytoregulatory sequelae are orchestrated in part through the interactive influences of a number of small leucine-rich proteoglycans (SLRPs), catabolism of which, for example during osteoarthritis (OA), may thereby detrimentally alter the biological and biophysical properties of the cartilage tissue. New findings reported in Arthritis Research & Therapy by Jordi Monfort and co-workers [1] provide an enhanced awareness of such processes by identifying a specific matrix metalloproteinase (MMP)-13 cleavage site in biglycan, and by assessing the ability of MMP-13 to degrade a number of SLRPs (biglycan, decorin, fibromodulin and lumican) present in normal and OA human cartilage extracts. Related studies also recently described in Arthritis Research & Therapy by Allan Young and colleagues [2] further highlight the susceptibility of cartilage SLRPs to proteolytic fragmentation during active progression of OA, thus concomitantly advocating the utility of monitoring SLRP catabolites as a promising biomarker strategy for evaluating OA disease status.Members of the SLRP gene family play vital roles in a variety of tissues and extracellular matrices, comprising binding and regulation of collagen fibrils, as well as modulation of cellular responses [3]. As exemplified by knockout mice [4], SLRP deficiencies in vivo lead to the development of corneal, dermatological and musculoskeletal diseases (including OA), indicating that the connate functions of SLRPs could be profoundly impacted by post-translational (i.e. proteolytic) processing events. Indeed, and with pertinent regard to this tenet, cleavage of decorin by MMP-2, MMP-3 and MMP-7 can result in the release of sequestered transforming growth factor-β, conceivably leading to patholo