Abstract
Microvesicles (MVs) mediate inter‐cellular communication by transferring cellular components to target cells, endowing them with an enhanced lipid and protein repertoire. We aimed to determine the function of neutrophil‐derived MVs in arthritis, as their concentration was augmented in synovial fluid of rheumatoid arthritis patients compared to paired plasma. Neutrophils adoptively‐transferred into arthritic mice migrated to inflamed joints and released MVs, observed abundantly within cartilage; the first evidence that MVs can penetrate cartilage matrix. Recent studies implicate TMEM16F as crucial for the exposure of phosphatidylserine on the cell surface, a key step in MV formation. Congruently, TMEM16F knockout mice released fewer neutrophil MVs and exhibited exacerbated cartilage damage in a model of inflammatory arthritis. Exogenous neutrophil MVs activated anabolic gene expression leading to extracellular matrix accumulation and cartilage protection. Mechanistic studies support a model whereby MV‐associated Annexin A1 interacts with its receptor FPR2/ALX, increasing TGF‐β production by chondrocytes, ultimately leading to cartilage protection. We envisage that MVs can be harnessed as a novel unique therapeutic strategy for the protection of cartilage and treatment of cartilage‐erosive diseases, where current therapy is completely lacking.
Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
