ITGB1-Mediated Focal Adhesion Signaling Underlies the Chondroprotective Effects of Extracorporeal Shockwave Therapy in Knee Osteoarthritis

Objective: To investigate the protective effect of extracorporeal shock wave therapy (ESWT) on knee osteoarthritis (KOA) and clarify its molecular mechanism, focusing on focal adhesion signaling. Design: KOA was induced in rats by anterior cruciate ligament transection, followed by ESWT once weekly for 4 sessions. Cartilage was analyzed by histology, immunohistochemistry, and extracellular matrix (ECM) marker expression. Primary chondrocytes were cultured to evaluate ESWT safety and effects on ECM metabolism. Bioinformatics analysis identified ITGB1 as a candidate regulator, and shRNA knockdown was used to test mechanistic involvement. Results: In vivo, ESWT preserved cartilage structure, enhanced Col2a1 and ACAN, and reduced MMP3/13 expression. In vitro, ESWT promoted ECM synthesis in chondrocytes and improved cytoskeletal remodeling. Bioinformatics showed ITGB1 downregulation in KOA cartilage and IL-1β–treated chondrocytes, which was restored by ESWT, reactivating focal adhesion kinase signaling. Silencing ITGB1 abolished ESWT-induced ECM synthesis and diminished cartilage protection. Conclusions: ESWT protects against KOA-associated cartilage degeneration by restoring ITGB1/FAK-mediated focal adhesion signaling in both animal and cellular models, rebalancing ECM metabolism, and supporting ESWT as a potential disease-modifying therapy.