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Purpose: Our previous work demonstrated that miRNA-495 targets SOX9 to inhibit chondrogenesis of mesenchymal stem cells. In this study, we aimed to investigate whether miRNA-495-mediated SOX9 regulation could be a novel therapeutic target for osteoarthritis(OA) using an in vitro cell culture model. Materials and Methods: An in vitro model mimicking the OA environment was established using TC28a2 normal human chondrocytecells. Interleukin-1β (IL-1β, 10 ng/mL) was utilized to induce inflammation-related changes in TC28a2 cells. Safranin Ostaining and glycosaminoglycan assay were used to detect changes in proteoglycans among TC28a2 cells. Expression levels ofCOX-2, ADAMTS5, MMP13, SOX9, CCL4, and COL2A1 were examined by qRT-PCR and/or Western blotting. Immunohistochemistrywas performed to detect SOX9 and CCL4 proteins in human cartilage tissues obtained from patients with OA. Results: miRNA-495 was upregulated in IL-1β-treated TC28a2 cells and chondrocytes from damaged cartilage tissues of patientswith OA. Anti-miR-495 abolished the effect of IL-1β in TC28a2 cells and rescued the protein levels of SOX9 and COL2A1, whichwere reduced by IL-1β. SOX9 was downregulated in the damaged cartilage tissues of patients with OA, and knockdown of SOX9abolished the effect of anti-miR-495 on IL-1β-treated TC28a2 cells. Conclusion: We demonstrated that inhibition of miRNA-495 alleviates IL-1β-induced inflammatory responses in chondrocytesby rescuing SOX9 expression. Accordingly, miRNA-495 could be a potential novel target for OA therapy, and the application ofanti-miR-495 to chondrocytes could be a therapeutic strategy for treating OA.
