miR-223 in exosomes from bone marrow mesenchymal stem cells ameliorates rheumatoid arthritis via downregulation of NLRP3 expression in macrophages

Background: Rheumatoid arthritis (RA) is an autoimmune disease with major clinical manifestations of human limb joint invasion, joint synovitis, and symmetrical lesions. In recent years, bone marrow mesenchymal stem cells (BMSCs) have been found to have low immunogenicity and immunomodulatory effects, which can regulate other types of cells through exosomes. However, the effect of BMSCs on immune response in the progression of RA has not been fully elucidated. Aims: The current research aimed to investigate the therapeutic effect of microRNA (miR)-223 in exosomes secreted by BMSCs on immune response in the progression of RA. Methods: Firstly, BMSCs were isolated and extracted, and then the influence of BMSCs on the level of inflammatory cytokines was detected by enzyme linked immunosorbent assay (ELISA). Exosomes from BMSCs were extracted and characterized. Some key autoimmune response genes and their protein products were detected in vivo and in vitro by real-time quantitative PCR, western blot and ELISA. Finally, the targeting relationship between miR-223 and NLR family pyrin domain-containing 3 (NLRP3) was predicted by bioanalytical software and verified by luciferase reporter assay and rescue experiments in vitro. Results: Exosomes from BMSCs could inhibit the release of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF alpha), and interleukin-18 (IL-18), and NLRP3 activation in macrophages and RA rats. In addition, we predicted online that miR-223 could target NLRP3 and provided a possible regulation pathway for the anti-inflammatory effects of BMSCs-secreted exosomes. Furthermore, we further confirmed that miR-223 could target and inhibit the expression of NLRP3. Conclusion: Taken together, these findings suggest that miR-223 carried by BMSCs-derived exosomes targets NLRP3 to regulate the activation of inflammasomes, which therefore can be served as a possible therapy for RA.