MicroRNA-497-5p attenuates IL-1β-induced cartilage matrix degradation in chondrocytes via Wnt/β-catenin signal...

Osteoarthritis (OA) is a degenerative joint disease. Degradation of extracellular matrix (ECM) in chondrocytes is closely related to joint destruction in OA progression. MicroRNAs (miRNAs) have been reported to play important roles in progression of OA. However, the roles of miR-497-5p in OA process and its underlying mechanism remain not been well established. Chondrocytes were obtained from articular cartilage and stimulated with IL-1β. The expression of miR-497-5p and Wnt3a was detected by qRT-PCR. Western blot analysis was performed to measure the proteins of Wnt3a, collagen II, aggrecan matrix metalloproteinase (MMP) 13 and ADAMTS4. Cell apoptosis was detected by flow cytometry. The putative binding sites of miR-497-5p and Wnt3a were predicted by Targetscan and verified through luciferase report assay. We found that miR-497-5p expression was reduced and Wnt3a expression was enhanced in OA cartilage and IL-1β-stimulated chondrocytes. Moreover, Wnt3a was a direct target of miR-497-5p, and expression of miR-497-5p was negatively correlated with Wnt3a level in OA cartilage. Furthermore, overexpression of miR-497-5p prominently increased the expression of cartilage matrix molecules collagen II and aggrecan, and reduced the expression of matrix-degrading enzymes MMP13 and ADAMTS4 while overexpression of Wnt3a reversed these effects, whereas addition of DKK-1attenuated the Wnt3a-mediated functions in IL-1β-stimulated chondrocytes. In conclusion, miR-497-5p attenuated IL-1β-induced cartilage matrix degradation in chondrocytes via Wnt/β-catenin signal pathway, providing a potential therapeutic target for treatment of OA.