RESUMEN

Objective @#To investigate the effect and mechanism of methyltransferase-like 3 (METTL3) on the pro- liferation , migration , and secretion of inflammatory factors by synovial fibroblasts from rheumatoid arthritis (RA) .@*Methods @#The expression of METTL3 in synovial tissue (SF) from 25 patients with rheumatoid arthritis and 25 pa- tients with osteoarthritis was detected by RT-qPCR and immunohistochemistry , respectively . The concentration of RNA m6A was detected by ELISA . RA synovial fibroblasts were isolated and cultured , and divided into NC ( nor- mal control) group , hi-METTL3 (overexpression of METTL3) group , si-METTL3 (knock-down METTL3) group , and STM2457 (METTL3 specific inhibitor) intervention group . Cell proliferation was detected by CCK-8 method . Apoptosis was detected by flow cytometry . And the concentrations of interleukin-6 ( IL-6) , interleukin-17A ( IL- 17A) , receptor activator of nuclear factor-kappa B ligand (RANKL) , and osteoprotegerin (OPG) in the superna- tant of cell culture were detected by ELISA . @*Results @#Compared with synovial tissue of osteoarthritis , the expres- sion of mRNA m6A and METTL3 in synovial tissue of RA significantly increased (P < 0. 05) . After overexpression of METTL3 , the expression of m6A in synovial fibroblasts increased . The proliferation and migration abilities of SF in hi-METTL3 group were significantly improved , and their apoptosis did not change significantly . The secretion of cytokines IL-6 and RANKL of SF in hi-METTL3 group significantly increased , while the OPG significantly de- creased (P < 0. 05) . After interfering with METTL3 expression , the expression of m6A in synovial fibroblasts de- creased . Cell proliferation and migration of SF in siMETTL3 group significantly decreased . The secretion of cyto- kines IL-6 and RANKL significantly decreased , and OPG significantly increased ( P < 0. 05) . After intervention with METTL3 inhibitor STM2457 , the proliferation and migration of synovial fibroblasts were significantly reduced , and the secretion of cytokines IL-6 and RANKL significantly reduced , and OPG significantly increased ( P < 0. 05) . There was no significant difference in the expression of IL-17A among each group . @*Conclusion @#METTL3 may promote the proliferation and migration of RA synovial fibroblasts , enhance the expression of IL-6 and RANKL , and inhibit the expression of OPG through RNA m6A methylation modification .