Extracellular vesicles in cartilage homeostasis, osteoarthritis, and biomarker discovery.

Abstract

Osteoarthritis (OA) is a chronic degenerative disease of the joint, involving cartilage degradation, synovial inflammation, and subchondral bone remodeling. Extracellular vesicles (EVs)-membrane-bound particles released by cells and have emerged as key mediators of intercellular communication in joint homeostasis and OA pathogenesis. EVs facilitate crosstalk between chondrocytes, synovial fibroblasts, and mesenchymal stem cells (MSCs), influencing joint health and disease progression. In OA, EV cargo: including proteins, miRNAs, and lipids, undergoes pathological changes that promote inflammation, matrix degradation, senescence, and calcification. Recent studies demonstrate that OA-derived EVs can induce catabolic and pro-inflammatory responses in recipient cells, while EVs from therapeutic sources such as MSCs, exhibit chondroprotective and anti-inflammatory effects in preclinical models. Additionally, EV surface markers and cargo profiles correlate with OA severity and pain, supporting their utility as minimally invasive biomarkers for early diagnosis and patient stratification. Cross-species comparisons suggest that EV signatures may be conserved, highlighting their translational potential in both human and veterinary medicine. However, the field is limited by variability in EV isolation and characterization methods, which hampers reproducibility and clinical application. To advance the clinical translation of EVs, standardized workflows and a deeper mechanistic understanding of EV function in the joint are essential. Identifying disease-specific EV biomarkers could enable earlier OA diagnosis and personalized treatment strategies, while optimizing therapeutic EVs could support regenerative approaches to slow or reverse joint degeneration and improve outcomes for human patients.