Research progress of exercise delaying the development of osteoarthritis by regulating pyroptosis
10.3760/cma.j.cn121113-20241025-00588
- VernacularTitle:运动通过调控细胞焦亡延缓骨关节炎进展的研究
- Author:
Dongfeng WAN
1
;
Manling LI
;
Xi CHEN
Author Information
1. 上海师范大学天华学院健康学院，上海 201805
- Publication Type:Journal Article
- Keywords:
Exercise therapy;
Osteoarthritis;
Pyroptosis;
Chondrocytes;
Synovial fibroblasts
- From:
Chinese Journal of Orthopaedics
2025;45(14):960-966
- CountryChina
- Language:Chinese
-
Abstract:
Osteoarthritis is a chronic degenerative disease characterized by cartilage degeneration, synovial inflammation, and subchondral bone remodeling. Its pathogenesis involves multiple links such as joint mechanical stress imbalance, extracellular matrix degradation, and inflammatory responses. Physical exercise has been widely recognized in the treatment of osteoarthritis. Although mechanism of action remains incompletely understood, appropriate exercise can effectively relieve pain caused by osteoarthritis, improve joint dysfunction, and reduce inflammation. In recent years, pyroptosis has been proven to exacerbate the pathological process of osteoarthritis by promoting the release of pro-inflammatory factors such as IL-1β and HMGB1 from synovial fibroblasts (FLSs) and chondrocytes. The pyroptosis of FLSs is regulated by the NLRP1/3 inflammasome, HIF-1α, and the SDF-1/AMPK pathway. In contrast, chondrocyte pyroptosis is closely related to the activation of the P2X7 receptor, the NF-κB/NLRP3 signaling axis, microRNAs (for example, miR-140-5p inhibits CTSB/NLRP3, while miR-155 promotes pyroptosis), and certain traditional Chinese medicine extracts (such as morroniside and loganin). Both exercise and pyroptosis are closely associated with the inflammatory response in osteoarthritis. Recent studies have found that exercise/mechanical stress stimulation can directly or indirectly regulate chondrocyte pyroptosis and delay the progression of osteoarthritis. In terms of direct regulation, moderate-intensity exercise can downregulate the expression of the P2X7 receptor, activate the AMPK/mTOR pathway to promote autophagy, and thereby inhibit chondrocyte pyroptosis. Mechanical stretch stimulation can upregulate TGF-β1 to activate the Smad2/3 pathway and inhibit the NF-κB/NLRP3 signaling axis. In terms of indirect regulation, exercise can inhibit the PI3K/Akt/NF-κB pathway by increasing the secretion of irisin, and simultaneously promote the production of lipoxin A4 (LXA4) to induce the polarization of synovial macrophages into the anti-inflammatory M2 type. In addition, exercise can also upregulate the expression of Metrnl protein and block the NLRP3/caspase-1/GSDMD pyroptosis signaling cascade.
