Decoding the therapeutic potential of extracellular vesicles in osteoarthritis: from biomolecular composition to clinical translation.

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder that substantially compromises the quality of life in middle-aged and elderly individuals. Conventional therapeutic approaches exhibit limited efficacy, and there is an urgent need to identify more effective treatment options. Extracellular vesicles (EVs) serve as essential mediators of intercellular communication and have been established as crucial carriers for the delivery of bioactive molecules, encompassing DNA, RNA species (including mRNAs, lncRNAs, microRNAs), proteins, and lipids, in the pathogenesis and repair of OA. Comprehensive research has demonstrated that EVs derived from diverse sources possess significant therapeutic potential in mitigating OA progression. However, their dual role in simultaneously facilitating the transport of both beneficial and harmful factors necessitates a cautious interpretation. This review aims to systematically investigate the roles of EVs derived from various origins and subpopulations in mitigating OA progression, summarize recent advancements in EV delivery methodologies, and emphasize emerging strategies to enhance their therapeutic specificity and efficacy. By elucidating these mechanisms, this review seeks to address translational challenges and provide valuable insights into the development of next-generation EV-based therapeutics for OA treatment.