Mediation of Cartilage Matrix Degeneration and Fibrillation by Decorin in Post‐traumatic Osteoarthritis
Qing Li, Biao Han, Chao Wang, Wei Tong, Yulong Wei, Wei‐Ju Tseng, Li‐Hsin Han, Li‐Hsin Han, X. Sherry Liu, Motomi Enomoto‐Iwamoto, Robert L. Mauck, Ling Qin, Renato V. Iozzo, David E. Birk, Lin Han, Lin Han
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.