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

Abstract

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. 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. 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. 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.