Temporomandibular joint osteoarthritis (TMJ-OA) is a progressive degenerative disease with limited effective treatments. In a randomized clinical trial, the authors demonstrated that administering autologous circulating extracellular vesicles (C-EVs) enhanced condylar bone regeneration, reduced symptoms, and reestablished joint homeostasis compared with standard hyaluronic acid therapy, with no adverse effects. Compared to EVs derived from TMJ-OA joint fluid, C-EVs were enriched in C1q binding protein (C1QBP) and exhibited regenerative and immunomodulatory properties. Mechanistic analysis revealed that C1QBP-high EVs targeted senescent chondrocytes, activating a C1q/C1QBP/p14ARF cascade that induced apoptosis in senescent cells and supported tissue repair and metabolic balance within the joint.
This article provides clinical evidence that circulating extracellular vesicles can act as a novel biological therapy for TMJ-OA by selectively clearing senescent cells and promoting regeneration, offering a promising new approach for treating degenerative joint disorders where current options are limited.
