Effect of Duhuo Jisheng Decoction on miRNA-17-5p Expression and PI3K/Akt/mTOR/GSDMD Signaling Pathway in a Rat Model of Knee Osteoarthritis

Abstract

Knee osteoarthritis (KOA) is a prevalent chronic knee joint disease characterized by cartilage degeneration and joint damage, with pain and joint deformity as the primary clinical manifestations. Emerging literature indicates that pyroptosis plays a pivotal role in the progression of KOA. Traditional Chinese medicine (TCM), especially Duhuo Jisheng Decoction has exhibited anti-inflammatory and analgesic potential in the treatment of KOA. However, it remains unclear whether it can affect pyroptosis and the underlying mechanisms. In this study, we established a rat model of KOA, and the Lequesne MG score confirmed the successful establishment of the arthritis model, demonstrating the therapeutic efficacy of Duhuo Jisheng Decoction in KOA treatment. Histopathological analysis showed a reduction in pathological damage to the synovial tissue of knee joints in Duhuo Jisheng Decoction treatment groups. Moreover, Duhuo Jisheng Decoction exhibited a regulatory effect on inflammatory factors in joint effusion. Consistent beneficial effects of Duhuo Jisheng Decoction were also observed in IL-1β induced SW1353 cells in vitro. We found that Duhuo Jisheng Decoction upregulated the expression of miR-17-5p. Both Duhuo Jisheng Decoction or overexpression of miR-17-5p can suppress the activation of PI3K/AKT/mTOR signaling pathway, thereby inhibiting the cleavage of GSDMD invlovled in pyroptosis. Together, our results suggest that Duhuo Jisheng Decoction regulates the PI3K/Akt/mTOR signaling pathway via miRNA-17-5p, thereby affecting the expression of pyroptosis key protein GSDMD. These findings contribute to our understanding of the relevant mechanisms in the treatment of KOA and provide insights into the application of TCM in managing KOA.