Effect of Acupotomy Modulation of NLRP3/Caspase-1/GSDMD Pathway on Chondrocyte Pyroptosis in Knee Osteoarthritis.

Background: Knee osteoarthritis (KOA) is a prevalent degenerative joint disease characterized by progressive cartilage degradation and inflammation, often leading to pain and reduced mobility. Current therapeutic approaches, including pharmacological and surgical interventions, provide symptomatic relief but rarely address the underlying pathological mechanisms effectively. Acupotomy therapy, a minimally invasive technique integrating traditional Chinese medicine and modern surgical concepts, has shown promise in alleviating KOA symptoms. However, its mechanisms, particularly concerning chondrocyte pyroptosis, remain underexplored. This study investigates the role of acupotomy therapy in modulating chondrocyte pyroptosis via the NLRP3/Caspase-1/GSDMD signaling pathway in a rabbit KOA model. Methods: Forty New Zealand rabbits were randomized into four groups: control, model, acupotomy, and drug-treated groups. A KOA model was induced via intra-articular injection of papain. Interventions included acupotomy therapy and oral celecoxib. Outcomes were assessed using behavioral scoring, micro-CT imaging, histological staining, serum inflammatory markers (ELISA), and the expression of NLRP3 inflammasome-associated proteins (qPCR and Western blot). Results: Acupotomy therapy significantly improved behavioral scores and reduced knee joint space narrowing. Histological analyses revealed improved cartilage integrity and decreased inflammatory markers. Expression levels of NLRP3, Caspase-1, ASC, and GSDMD were downregulated in the acupotomy group compared to the model group. Conclusion: This study highlights the therapeutic potential of acupotomy therapy in alleviating KOA symptoms and reducing chondrocyte pyroptosis by modulating the NLRP3 inflammasome pathway. These findings provide a mechanistic basis for its application in KOA treatment and a foundation for further clinical exploration.