Polydatin Protects Against Articular Cartilage Degeneration by Regulating Autophagy Mediated by AMPK/Mtor Signaling Pathway

Abstract

Background: Knee osteoarthritis (KOA) is one of the leading causes of disability, and its etiopathogenesis is not completely understood. Polydatin has the potential effect on the treatment of KOA, but the mechanism is not clear.Methods: After an KOA rat model was established by anterior cruciate ligament transection, KOA rats were treated with polydatin (4 mg/kg) for 30 days. Subsequently, cartilage tissues were collected from rats and detected by HE, TUNEL staining and Western blotting to evaluate the pathological damage, apoptosis and autophagy activity. Then, human chondrocyte C28/I2 cells were stimulated by LPS to induce a KOA model in vitro, and the effects of polydatin on the C28/I2 cell viability, apoptosis and autophagy were also detected. In addition, the mechanism of polydatin on KOA in C28/I2 cells was investigated, and the effect of an AMPK inhibitor (Dorsomorphin 2HCl) on the proliferation and apoptosis of polydatin administrated-cells were also detected. Results: After treated with polydatin, the pathological damage of rat cartilage tissues were ameliorated, cells apoptosis was inhibited and autophagy was activated in KOA rats. Meanwhile, polydatin also ameliorated the proliferation and apoptosis of C28/I2 cells, the expression of autophagy-related proteins, LC3II/LC3I, Beclin-1, and p-AMPK/AMPK were up-regulated, p-mTOR/mTOR was down-regulated by polydatin in C28/I2 cells. Interestingly, relative results showed that the improvement effect of polydatin on LPS-sdtimulated-C28/I2 cells was blocked by AMPK/mTOR inhibitor, Dorsomorphin 2HCl. Conclusion: Our research showed that polydatin reduces apoptosis and activate autophagy both in a rat model of KOA and C28/I2 cell model by AMPK/mTOR signaling pathway, which provides the basis for further investigations into the potential therapeutic impact of polydatin in KOA.