The dual role of extracellular vesicles in OA: Pathological mediators, diagnostic biomarkers, and therapeutic targets

Osteoarthritis (OA) remains a formidable global health challenge, characterized by progressive articular cartilage degradation and a lack of effective disease-modifying interventions. Extracellular vesicles (EVs), previously categorized as mere cellular debris, have recently emerged as pivotal orchestrators of intercellular communication within the joint microenvironment. This review critically examines the dichotomous nature of EVs in OA. We characterize how endogenous EVs from stressed joint tissues drive pathology by disseminating pro-inflammatory and catabolic signals. Conversely, we highlight the therapeutic promise of exogenous EVs-particularly those derived from mesenchymal stem cells-as potent, cell-free regenerative agents capable of immunomodulation and cartilage repair. Beyond their biological roles, we discuss the emerging utility of synovial fluid EVs as liquid biopsies for early diagnosis and disease stratification. Finally, we address key translational bottlenecks, which demand standardization according to Minimal Information for Studies of Extracellular Vesicles 2023 (MISEV2023) to accelerate clinical application.