Background Rheumatoid Arthritis (RA) is a systemic autoimmune disorder characterized by chronic synovitis and progressive joint destruction. MicroRNAs (miRNAs) are small non-coding RNA molecules able to modulate gene expression at post-transcriptional level. Different miRNAs, potentially involved in the control of genes related to inflammatory pathways or immunological activation, have been found to be strongly up-regulated in RA. In particular miR-146a and -155 have been found up-regulated in synovial tissue (ST) and synovial fibroblasts (FLS) (1). Recently we have described the over-expression of miR-223 in CD3+ cells extracted from blood and synovial fluid of patients affected by active RA (2), even in the early phase of the disease (3). No information is available about miR-223 expression in RA ST as yet.
Objectives To test the expression of miR-223 in ST from RA patients compared with normal and osteoarthritis (OA) individuals. In addition, to test the expression of miR-146 and -155 in ST of the same patients.
Methods ST was obtained from 16 RA patients, 5 OA patients, and 5 joint trauma patients (healthy control specimens). Informed consent was obtained from all patients, and RA patients fulfilled the ACR criteria for classification of the disease. Three ST specimens were obtained from random sites during surgery. Tissues were snap-frozen and stored at -80°C. Samples were homogenized with Tissue Lyser and total RNA was obtained from each sample by using miRNeasy system (Qiagen). The expression of miR-223, -146a and -155 was analyzed by qPCR following miscript PCR system (Qiagen). A non-parametric test (Kruskall Wallis) was used to perform statistical analysis.
Results We found an overexpression of miR-146 in RA synovia in comparison to healthy donors (2,35±0,73 vs 0,75±0,17) and OA (1,87±0,41) (p<0,05). An increase of miR-155 was also found but the difference with OA ST was not statistically significant. (1,38±0,68 vs 0,91±0,44). miR-223 was found to be increased in RA ST compared to OA but also in this case the difference was not significant (1,95±0,78 vs 1,48±0,15).
Conclusions In our study we have confirmed that miR-146a and -155 are overexpressed in ST of RA patients. In particular, the expression of miR-146a was found significantly increased in RA compared to synovial membrane from healthy donors. Of note our preliminary data have shown, for the first time, that miR-223 is detectable in RA ST and that its level is higher than in OA. Further studies are needed to confirm the hypothesis of a role for miR-223 in the pathogenesis of RA.
This work is supported by FIRA onlus 2009 (Fondazione Italiana per la Ricerca sull’Artrite) and Regione Toscana Progetto POR CReO FESR 2007-2013.
Stanczyk J, Pedrioli DM, Brentano F, et al. Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum. 2008;58(4).
Sebastiani GD, Fulci V, Niccolini S, et al. Over-expression of miR-223 in T-lymphocytes of early rheumatoid arthritis patients. Clin Exp Rheumatol. 2011;29:1058-1059.
Disclosure of Interest None Declared