From pathogenic to reparative: Context-Dependent function of extracellular vesicles in osteoarthritis.

Osteoarthritis (OA) is a whole-joint disease characterized by progressive structural degeneration and chronic low-grade inflammation affecting the cartilage, synovium, subchondral bone, and immune compartments. It is a complex degenerative disorder associated with substantial morbidity, heterogeneous clinical trajectories, and limited disease-modifying treatment options. Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication within the OA joint microenvironment, and are implicated in pathophysiological responses to mechanical stress, inflammatory cues, and metabolic dysfunction. Through the transfer of context-dependent nucleic acid, protein, and lipid cargoes, EVs can amplify pathogenic processes in OA such as synovitis, cartilage catabolism, and cellular senescence, while also supporting reparative pathways. Understanding the mechanisms governing EV biogenesis, cargo selection, tissue targeting, and functional heterogeneity offers opportunities to identify mechanistically informed biomarkers and therapeutic strategies. This review discusses emerging concepts in EV-mediated joint communication, highlights translational potential and limitations, and outlines key priorities for advancing EV-based diagnostics and therapies in OA. However, EV-based strategies remain largely at the preclinical or experimental stage, and rigorous validation is required before they can enter routine clinical practice.