Inhibition of microRNA-21 decreases the invasiveness of fibroblast-like synoviocytes in rheumatoid arthritis via TGFβ/Smads signaling pathway

Objective(s): MicroRNA-21 (miR(21)) is aberrantly elevated in rheumatoid arthritis (RA) patients, the significance of this microRNA in RA pathogenesis and treatment, however, has not been investigated. In this study, by using RA-derived fibroblast-like synoviocyte (FLS) cells as a model, we investigated the effect and corresponding mechanism of miR(21) inhibition on FLSs invasion. Materials and Methods: miR(21) expression in synovial tissue and FLSs in RA patients and non-RA controls were determined by stem-loop RT-PCR. The effect of miR(21) on FLSs viability and invasiveness were evaluated using miR(21) inhibition. Cell viability was evaluated by MTT assay and the expression of genes at mRNA and protein levels was determined by RT-PCR and Western blot, respectively. Results: Our results showed that miR(21) expression was highly increased in synovial tissue and FLSs in RA patients. Also, we reported that miR(21) inhibitor treatment could significantly suppress the invasiveness of FLSs without affecting cell viability. The decreased FLSs invasion by miR(21) inhibition was associated with down-regulated expression of matrix metalloproteinase (MMP)-1, MMP3, and MMP13. Further analysis revealed that miR(21) inhibition could suppress the expression of TGF(beta 1) and Smad(4), but promote that of Smad(7). Moreover, suppression of FLS invasion and MMPs expression by miR(21) treatment could be counteracted by additional TGF(beta 1) treatment. Conclusion: Our results indicated that miR(21) inhibition can down-regulate the expression of MMP1, MMP3, and MMP13 and consequently suppress the invasiveness of FLS, which is achieved through TGF(beta 1)/Smad(4/7) signaling pathway. The findings of this study could offer a novel approach for RA treatment.