The "skeletal muscle-cartilage unit" in knee osteoarthritis: from mechanical coupling to molecular mechanisms

Knee osteoarthritis (KOA) is a degenerative joint condition substantially influenced by the surrounding musculature. Skeletal muscle and articular cartilage form an integrated "skeletal muscle-cartilage unit" crucial for maintaining joint homeostasis. This review seeks to elucidate the biomechanical and molecular connections within the skeletal muscle-cartilage unit and their relevance to the development and management of KOA. Skeletal muscle failure, characterized by atrophy, compromises knee biomechanics. This atypical mechanical stress is transmitted by mechanosensitive ion channels (e.g., Piezo1, TRPV4) on chondrocytes, resulting in matrix degradation. At the same time, pathological skeletal muscle functions as an altered endocrine organ. Dysregulated myokine synthesis (elevated IL-6, less irisin) and the activation of shared pathways, such as NF-κB, substantially modify the local microenvironment. Conversely, restoring optimum muscle function can significantly reduce the generation of inflammatory mediators and protect cartilage integrity. Modifying this axis through evidence-based exercise treatment efficiently restores joint alignment, enhances physiological mechanical stress, and diminishes pro-inflammatory signals. Future research examining the relationship between exercise therapy, skeletal muscle secretion, and cartilage homeostasis holds significant promise for the enhancement of targeted KOA therapies.