Mediation of Cartilage Matrix Degeneration and Fibrillation by Decorin in Post‐traumatic Osteoarthritis

Abstract

Objective To elucidate the role of decorin, a small leucine‐rich proteoglycan, in the degradation of cartilage matrix during the progression of post‐traumatic osteoarthritis ( OA ). Methods Three‐month–old decorin‐null (Dcn −/− ) and inducible decorin‐knockout (Dcn i KO ) mice were subjected to surgical destabilization of the medial meniscus ( DMM ) to induce post‐traumatic OA . The OA phenotype that resulted was evaluated by assessing joint morphology and sulfated glycosaminoglycan ( sGAG ) staining via histological analysis (n = 6 mice per group), surface collagen fibril nanostructure via scanning electron microscopy (n = 4 mice per group), tissue modulus via atomic force microscopy–nanoindentation (n = 5 or more mice per group) and subchondral bone structure via micro–computed tomography (n = 5 mice per group). Femoral head cartilage explants from wild‐type and Dcn −/− mice were stimulated with the inflammatory cytokine interleukin‐1β ( IL ‐1β) in vitro (n = 6 mice per group). The resulting chondrocyte response to IL ‐1β and release of sGAG s were quantified. Results In both Dcn −/− and Dcn i KO mice, the absence of decorin resulted in accelerated sGAG loss and formation of highly aligned collagen fibrils on the cartilage surface relative to the control ( P < 0.05). Also, Dcn −/− mice developed more salient osteophytes, illustrating more severe OA . In cartilage explants treated with IL ‐1β, loss of decorin did not alter the expression of either anabolic or catabolic genes. However, a greater proportion of sGAG s was released to the media from Dcn −/− mouse explants, in both live and devitalized conditions ( P < 0.05). Conclusion In post‐traumatic OA , decorin delays the loss of fragmented aggrecan and fibrillation of cartilage surface, and thus, plays a protective role in ameliorating cartilage degeneration.