The nexus of mechanical stress, integrin signaling, and endocytosis in osteoarthritis

Osteoarthritis (OA) is a degenerative disease characterized by cartilage degeneration and joint structural damage, with its pathogenesis closely associated with abnormal mechanical stress, cellular signaling, and inflammatory responses. As key mechanosensors, integrins are involved in cell adhesion, cytoskeletal regulation, and inflammatory processes, and their endocytosis and recycling further modulate cellular functions. Studies show that abnormal mechanical stress can accelerate cartilage matrix degradation and inflammation through integrin-mediated signaling and endocytic pathways. Meanwhile, various integrin-targeted interventions, including small molecule drugs, natural bioactive compounds, and Arg-Gly-Asp (RGD) functionalized biomaterials, have demonstrated chondroprotective and therapeutic potential. These findings highlight integrins and their endocytic regulation as promising research directions in OA pathogenesis and potential therapeutic targets. This review summarizes the signaling mechanisms of integrins in OA, with a particular focus on the interaction between mechanical stress and integrins, as well as the potential role of integrin endocytosis in OA pathology, and discusses drug and biomaterial-based therapeutic strategies targeting integrins.