SOX9 promotes proliferation of fibroblast-like synoviocytes in rheumatoid arthritis by inhibiting miR-204/-211

ObjectiveTo investigate the effect of sex determining region Y-box transcription factor 9 (SOX9) on the function of fibroblast-like synoviocyte (FLS) in rheumatoid arthritis (RA) by inhibiting micro-ribonucleic acid (miRNA)-204 and -211, and to explore the underlying mechanism. MethodsA collagene-induced arthritis (CIA) model was established by type Ⅱ collagen induction. FLS were isolated from the knee joint synovial tissue of CIA mice by digestion with type Ⅳ collagenase. The expression level of Sox9 in FLS was detected by quantitative real-time polymerase chain reaction (qPCR). Small interfering ribonucleic acid (siRNA) was used to inhibit Sox9 expression, and cell proliferation was assessed by CCK-8 assay and 5-ethynyl-2’-deoxyuridine (EdU) staining. Cell senescence was analyzed by senescence-associated β-galactosidase (SA-β-gal) staining, and the expression of cyclin-dependent kinase inhibitor (CKI) p16, p21, p53 and miR-204, miR-211 was detected by qPCR. The HDOCK online server (http://hdock.phys.hust.edu.cn/) was used to analyze the binding potential between miR-204/miR-211 and SOX9. ResultsCompared with FLS from normal mice, the messenger ribonucleic acid (mRNA) level of SOX9 was significantly increased in CIA-FLS. Knock down of Sox9 can promote cell senescence, thereby inhibiting FLS proliferation. Both miR-204 and miR-211 could stably bind to SOX9. Knockdown of Sox9 in CIA-FLS can increase the expression of miR-204/-211. ConclusionsSOX9 can promote the proliferation of CIA-FLS and inhibit their senescence by down-regulating the expression of miR-204 and miR-211.