Exosomes derived from platelet-rich plasma alleviate synovial inflammation by enhancing synovial lymphatic function

Abstract

Background: Synovial inflammation is a pivotal factor in the pathogenesis of osteoarthritis (OA). Platelet-rich plasma-derived Exosomes (PRP-Exos), known for their low immunogenicity, have demonstrated efficacy in modulating chondrocyte function. However, the specific effects and mechanisms of PRP-Exos in synovial inflammation remain unclear. This study aimed to investigate the therapeutic effects and mechanisms of PRP-Exos in synovial inflammation induced by destabilization of the medial meniscus (DMM) in mice. Results: PRP-Exos were extracted via ultracentrifugation. In vivo experiments revealed that PRP-Exos alleviated pain behaviors and synovial inflammation in DMM mice. Furthermore, it was discovered that PRP-Exos enhanced the synovial lymphatic function in DMM mice and promoted lymphangiogenesis. Meanwhile, the therapeutic effect of PRP-Exos on synovial inflammation was attenuated after inhibition of lymphatic function. In vitro studies demonstrated that PRP-Exos enhanced the proliferation, migration, and tube formation ability of lymphatic endothelial cells (LECs), via regulating the PI3K/Akt signaling pathway. Conclusions: This research is the first to reveal that PRP-Exos alleviate pain behaviors and synovial inflammation in DMM mice through activation of the PI3K/Akt signaling pathway in LECs, thereby enhancing synovial lymphatic function and promoting the clearance of inflammatory cells and associated cytokines. These findings offer a novel theoretical foundation for the treatment of synovial inflammation and other inflammation-associated disorders.