Down‐regulation of miR‐10a‐5p in synoviocytes contributes to TBX5‐controlled joint inflammation

Micro RNA s are considered to play critical roles in the pathogenesis of human inflammatory arthritis, including rheumatoid arthritis ( RA ). The purpose of this study was to determine the relationship between miR‐10a‐5p and TBX 5 in synoviocytes and evaluate their contribution to joint inflammation. The expression of miR‐10a‐5p and TBX 5 in the synovium of RA and human synovial sarcoma cell line SW 982 stimulated by IL ‐1β was determined by RT ‐ qPCR and Western blotting. The direct interaction between miR‐10a‐5p and TBX 5 3′ UTR was determined by dual‐luciferase reporter assay in HeLa cells. Mimics and inhibitors of miR‐10a‐5p were transfected into SW 982 cells. TBX 5 was overexpressed by plasmid transfection or knocked down by RNA i. Proinflammatory cytokines and TLR 3 and MMP 13 expressions were determined by RT ‐ qPCR and Western blotting. Down‐regulated expression of miR‐10a‐5p and up‐regulation of TBX 5 in human patients with RA were found compared to patients with OA . IL ‐1β could reduce miR‐10a‐5p and increase TBX 5 expression in SW 982 cells in vitro . The direct target relationship between miR‐10a‐5p and 3′ UTR of TBX 5 was confirmed by luciferase reporter assay. Alterations of miR‐10‐5p after transfection with its mimic and inhibitor caused the related depression and re‐expression of TBX 5 and inflammatory factors in SW 982 cells. Overexpression of TBX 5 after pCMV 3‐ TBX 5 plasmid transfection significantly promoted the production of TLR 3, MMP 13 and various inflammatory cytokines, while this effect was rescued after knocking down of TBX 5 with its specific si RNA . We conclude that miR‐10a‐5p in a relation with TBX 5 regulates joint inflammation in arthritis, which would serve as a diagnostic and therapeutic target for RA treatment.