Paeoniflorin inhibits the inflammation of rheumatoid arthritis fibroblast-like synoviocytes by downregulating hsa_circ_009012

Abstract

Background Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to progressive joint damage. Circular RNAs (circRNAs) can regulate the inflammatory response of fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) and influence the disease progression. Paeoniflorin (PF) is the main active ingredient extracted from Paeonia lactiflora Pallas and is known for its anti-inflammatory effect. This study aims to explore the potential mechanisms by which hsa_circ_009012 and PF regulate the inflammatory response in RA. Methods RNA expression of hsa_circ_009012, has-microRNA-1286 (miR-1286), toll-like receptor 4 (TLR4), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) were assessed by real-time quantitative polymerase chain reaction (RT-qPCR) or western blotting (WB). Cell inflammation markers (TNF-α, IL-1β, IL-6) were assessed by RT-qPCR and immunofluorescence (IF). Counting Kit-8 (CCK-8) assay, flow cytometry, and transwell assay were utilized to test cell viability, cell cycle distribution, and migration. Results Hsa_circ_009012 was highly expressed in RA-FLSs. Hsa_circ_009012 overexpression facilitated the inflammation in RA-FLSs and was closely associated with the miR-1286/TLR4 axis. Paeoniflorin inhibited inflammation and the expression of hsa_circ_009012 and TLR4, while upregulating the expression of miR-1286 in RA-FLSs. Moreover, the upregulation of hsa_circ_009012 reversed the repressive effect of paeoniflorin on RA-FLSs progression. Conclusion Paeoniflorin inhibits the inflammation of RA-FLSs via mediating the hsa_circ_009012/miR-1286/TLR4/NLRP3 axis.