Overexpression Of Sox9 Alleviates The Progression Of Human Osteoarthritis In Vitro And In Vivo

Purpose: Recent findings have identified that SOX9 served as a key role during the pathogenesis of osteoarthritis (OA). This study aimed to investigate the mechanisms by which SOX9 regulated the formation of OA in vitro and in vivo.Materials and methods: The relative expressions of SOX9 in patients with OA and normal fracture of thighbone were analyzed by real-time-PCR. In vitro, IL-1 beta induced inflammatory response in human chondrocytes was used to evaluate the function of SOX9. The recombinant SOX9 lentivirus vector (Lenti-SOX9) was used to upregulate the expression of SOX9 in cells. ELISA was used to measure the concentration of tumornecrosis factor-alpha (TNF-alpha). The protein expressions of SOX9, matrixmetalloproteinase-13 (MMP13), Collagen II, Aggrecan and Smad3 were analyzed by Western blot. Cell proliferation and cell apoptosis were detected by CCK-8 assay and flow cytometry, respectively. In vivo, the effect of SOX9 on surgically induced OA mice was evaluated.Results: The gene level of SOX9 was remarkably downregulated in patients with OA compared with normal people, while the concentration of TNF-alpha was upregulated. In addition, IL-1 beta reduced the expressions of SOX9, Collagen II and Aggrecan and increased the level of MMP13 in chondrocytes. Moreover, Lenti-SOX9 notably inhibited IL-1 beta-induced growth inhibition and apoptosis in chondrocytes via increasing the expression of Smad3. Finally, Lenti-SOX9 markedly alleviated the symptoms of OA mice in vivo.Conclusion: Upregulation of SOX9 inhibited IL-1 beta-induced inflammatory response via increasing the level Smad3 in human chondrocytes and exhibited therapeutic effect on surgically induced OA mice in vivo. Therefore, SOX9 may serve as a potential target in the treatment of OA in the future.