Extracorporeal Shock Wave Alleviates Knee Contracture in Rats by Inhibiting Hypoxia-Mediated Pyroptosis in Joint Capsular Fibroblasts

Background: Joint immobilization frequently causes joint contracture, which may significantly impact an individual’s quality of life. Consequently, extracorporeal shock wave (ESW) has been increasingly adopted to manage various bone and joint diseases. Our study investigated whether ESW therapy relieves knee contracture and if it mitigates the underlying hypoxia-induced pyroptosis of joint-capsule fibroblasts. Methods: A rat model of knee contracture was established through prolonged unilateral knee joint immobilization. Following the application of ESW, the levels of joint capsule fibrosis and cell pyroptosis were evaluated. During the immobilization phase, the NOD-like receptor protein 3 (NLRP3) specific inhibitor MCC950 was administered to assess its impact on pyroptosis levels. In vitro, hypoxia-induced rat knee joint synovial fibroblasts were exposed to hypoxia to induce myofibroblast differentiation. Hypoxia-inducible factor 1 alpha (HIF-1α) small interfering RNA was then used to inhibit HIF-1α expression, followed by the measurement of cell pyroptosis and fibrosis levels. Results: ESW intervention successfully mitigated knee contracture while decreasing pyroptosis and fibrosis in the joint capsule. Similarly, MCC950 treatment effectively inhibited both pyroptotic cell death and fibrotic tissue development within the capsule. Hypoxia induced the differentiation of synovial fibroblasts into myofibroblasts and increased pyroptosis. However, inhibiting HIF-1α expression mitigates these effects, leading to reduced pyroptosis and fibrosis in rat knee synovial fibroblasts. Conclusions: Hypoxic conditions promote pyroptosis in rat knee synovial fibroblasts and drive their differentiation into myofibroblasts, contributing to joint contracture. ESW therapy may alleviate joint contractures by partially inhibiting structural and cellular changes.