MiR-223-3p inhibits inflammation and pyroptosis in monosodium urate-induced rats and fibroblast-like synoviocytes by targeting NLRP3.

Down-regulated miR-223-3p was found in rheumatoid arthritis. This study aimed to further explore the level and role of miR-223-3p in gout arthritis (GA). After monosodium urate (MSU)-induced GA rat and fibroblast-like synoviocytes (FLSs) model were established, the rats paw volume and gait score were documented and the FLSs were transfected with miR-223-3p mimic/inhibitor or NLRP3-overexpression plasmids. MiR-223-3p target was found through bioinformatics and dual-luciferase reporter. The pathological damage of rat joint was observed by hematoxylin-eosin staining. The levels of IL-1β, TNF-α, and articular elastase in rats were detected by ELISA. The viability and pyroptosis of FLSs were detected by MTT and flow cytometry. The expressions of miR-223-3p, NLRP3, Cleaved Caspase-1, IL-1β, ASC, and Cleaved N-terminal GSDMD in FLSs or rat synovial tissues were detected by RT-qPCR, immunofluorescence, Western blot, or immunohistochemistry analysis. MSU increased the paw volume, gait score, inflammation in synovial tissues, increased the levels of IL-1β, TNF-α, and articular elastase in rats. MSU decreased the viability and increased the pyroptosis of FLSs, up-regulated the expressions of NLRP3, ASC, Cleaved Caspase-1, Cleaved N-terminal GSDMD, and IL-1β, and down-regulated miR-223-3p expression in synovial tissues of rat joints and FLSs. MiR-223-3p mimic reversed the effect of MSU on lowering cell viability, increasing pyroptosis in FLSs, while miR-223-3p inhibitor further enhanced the effect of MSU on FLSs. NLRP3 was a target of miR-223-3p. Besides, NLRP3 overexpression reversed the effects of miR-223-3p on MSU-induced FLSs. MiR-223-3p inhibited pyroptosis in MSU-induced rats and FLSs by targeting NLRP3.