Targeting mechanotransduction components as therapeutic strategies in osteoarthritis.

Chondrocytes are exposed to millions of mechanical stimuli each day, making mechanotransduction central to cartilage physiology. Normal mechanical loading preserves extracellular matrix integrity and supports anabolic activity, whereas abnormal stresses shift signaling pathways toward catabolism, inflammation, and tissue degeneration, ultimately driving osteoarthritis (OA). Despite progress in pharmacological and surgical interventions, no current therapy can fully prevent or reverse OA progression. This gap underscores the importance of exploring the molecular mechanisms of mechanotransduction in search of novel disease-modifying strategies. This review highlights key mechanosensitive systems in chondrocytes—including ion channels, integrins, the cytoskeleton, primary cilia, and connexins—and discusses how their altered responses to inappropriate mechanical and inflammatory stimuli contribute to OA pathogenesis. A deeper understanding of these processes may open new avenues for targeted therapies aimed at restoring mechanical homeostasis in cartilage.