The Effects of Extracellular Vesicles from Senescent Cells in Osteoarthritis

In this study, we found that senescent chondrocytes isolated from OA patients secrete more EVs compared with nonsenescent chondrocytes. These EVs inhibit cartilage ECM deposition by healthy chondrocytes and can induce a senescent state in nearby cells. We profiled the miR and protein content of EVs isolated from the synovial fluid of OA joints from mice with SnCs. After treatment with a molecule to remove SnCs, termed a senolytic, the composition of EV-associated miR and protein was markedly altered. The senolytic reduced OA development and enhanced chondrogenesis, and these were attributable to several specific differentially expressed miRs (miR-30c, miR-92a, miR-34a, miR-24, miR-125a, miR-150, miR-186, and miR-223) and proteins (Serpina and aggrecan). In aged animals, treatment with senolytic modulated the inflammatory response by decreasing recruitment and activation of myeloid and phagocytic cells. Collectively, these findings suggest that altered levels of synovial EV miRs and proteins are a potential mechanism by which SnCs can transfer senescence, inhibit tissue formation, and promote OA development. When isolated from synovial fluid, EVs may also be used to predict therapeutic response to senolytic therapies in the articular joint.
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs