Mechanism of action of curcumin targeting TRPM2/NLRP3 signaling axis to mediate cell death in the treatment of knee osteoarthritis.

Abstract

Objects: This study intends to explore the possible mechanisms of curcumin's action after knee osteoarthritis.

Methods: Chondrocytes alone were used to mimic the cellular inflammatory response with interleukin IL-1β. Overexpressing TRPM2 chondrocytes were constructed using cell transfection technique for mechanism verification. The proliferation of chondrocytes was assessed by CCK8 assay, cellular ROS level was detected by flow cytometry, cellular inflammatory factor content was detected by ELISA kit, and molecules of cellular pyroptosis-related signaling pathway were detected by western blot and immunofluorescence. In vivo experiments, a rat knee osteoarthritis model was constructed. Cartilage integrity was assessed by histological analysis, cellular inflammatory factor content was detected by ELISA kit, and cellular pyroptosis-related signaling pathway molecules were detected by western blot and immunohistochemistry.

Results: Curcumin targeting the TRPM2/NLRP3 signaling axis significantly inhibited IL-1β induced decrease in cell viability, increase in ROS level, secretion of inflammatory factors such as TNF-α, IL-6, IL-10, etc., as well as decreased the expression of cellular scaffolding-related proteins, such as GSDMD, NLRP3 and pro-caspase-1, etc. (p < .05). Meanwhile, curcumin targeting the TRPM2/NLRP3 signaling axis also significantly improved the pathological state of cartilage tissue, maintained cartilage integrity, and reduced the secretion of inflammatory factors, and treated osteoarthritis of the knee in rats by mediating cellular pyroptosis.

Conclusions: Curcumin can effectively improve the inflammatory response of chondrocytes through the TRPM2/NLRP3 signaling axis in the treatment of osteoarthritis of the knee in rats.