Metabolic crosstalk between skeletal muscle and cartilage tissue: insights into myokines in osteoarthritis.

With the expansion of technology and the prevalence of a sedentary lifestyle, physical inactivity and a lack of desire to strengthen muscle tissue have led to the accumulation of large forces on the joints and the spread of joint-related diseases, including osteoarthritis (OA) in humans. This disease can significantly impair the quantity and quality of life of patients and impose a large financial burden on the healthcare community. Controlling and inhibiting the progression of this disease at the cellular level is a therapeutic strategy for OA. The spread of inflammation and the destruction of chondrocyte metabolism leads to cartilage damage. Chondrocytes are important cellular components of normal cartilage, and the destruction of these cells by apoptosis is considered a major factor in OA. The normal metabolism of these cells also plays an important role in the normal function of cartilage. Skeletal muscle tissue may assist in the control of inflammation through secreting peptides called myokines which can communicate with cartilage tissue and improve the function of cartilage cells. Myokines may therefore play a therapeutic role in OA by regulating the metabolism of chondrocytes. This review critically synthesizes emerging evidence on myokine-mediated muscle-cartilage crosstalk, highlighting unresolved mechanistic questions and therapeutic paradoxes. We propose a novel framework of classifying myokines as anabolic, catabolic, or context-dependent mediators, offering a roadmap for targeted OA interventions. Discrepancies between preclinical models and human studies, along with tissue-specific bioavailability challenges, are emphasized as key translational barriers.