AB0156 Altered Expression and Regulation of Microrna in Psoriatic Arthritis
Authors: S. Wade, M. Trenkmann, T. Mc Garry, D. Veale, U. Fearon
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Psoriatic Arthritis (PsA) is a chronic immune-mediated inflammatory disease, characterised by proliferation of synovial tissue, progressive destruction of articular cartilage/bone, and is associated with psoriasis. It is now evident that these processes may be governed by microRNA (miRNA), a class of small non-coding RNAs which exert their function through suppression of specific target genes. Altered miR23a∼27a∼24-2 cluster expression has been previously associated with angiogenic, pro-inflammatory mechanisms and osteoblast differentiation. Abnormal miRNA expression has been previously demonstrated in rheumatoid arthritis, however to date their expression and regulation has not been examined in PsA. <h3>Objectives</h3> To investigate if the miR-23a∼27a∼24-2 cluster contributes to PsA joint pathogenesis. <h3>Methods</h3> Synovial tissue biopsies and peripheral blood mononuclear cells (PBMC) from PsA (n=8/8) and osteoarthritis (OA) (n=5/7) patients were collected. Expression levels of miR-30b, miR-21-5p and cluster partners, miR-23a and miR-27a, were quantified using the miRNA isolation kit (Qiagen) and Sybr Green real-time PCR. To investigate potential factors involved in the regulation of miRNA expression in the joint, primary PsA synovial fibroblasts (SFC) were cultured with pro-inflammatory stimuli including (TLR) ligands: Pam3CSK4 (1μg/ml), LPS (1μg/ml), Poly I:C (1μg/ml) and pro-inflammatory cytokines: IL-6 (20ng/ml), IL-17 (50ng/ml), IL-23 (20ng/ml), TNF-α (10ng/ml) and IL-1β (1ng/ml) and examined for miRNA expression. <h3>Results</h3> A significant decrease in expression of miR-23a was demonstrated in PsA, compared to OA, synovial tissue (p&lt;0.05). Similarly, both miR-30b and miR-27a showed decreased expression in PsA synovium versus OA (both p&lt;0.065). In contrast, a significant increase in miR-23a expession was observed in PsA PBMC versus OA (p&lt;0.05). This is consistent with studies suggesting dissociation between systemic and local inflammation. TLR ligands PolyIC (TLR3) and LPS (TLR4) significantly decreased miR-27a expression in PsA SFC (all p&lt;0.05). In addition, PolyIC also significantly decreased miR-23a expression (p&lt;0.05). Furthermore, synovial tissue miR-23a expression was inversely associated with the degree of macroscopic joint vascularity and radiographic severity in PsA. Finally, <i>in silico</i> analysis was utilised to identify putative miR-23a∼27a∼24-2 targets including TRIF, SOCS6 and NRP2. <h3>Conclusions</h3> This is the first report to demonstrate altered expression and regulation of miRNA, at the site of inflammation, in PsA patients. PolyIC suppression of the miR-23a∼27a∼24-2 cluster may in turn impair their ability to suppress putative targets - TRIF, SOCS6 and NRP2, which are known to promote angiogenesis and persistent activation of inflammatory pathways. These data suggest a potential strategy for therapeutic targeting of miRNA in the treatment of PsA. <h3>Disclosure of Interest</h3> S. Wade: None declared, M. Trenkmann: None declared, T. Mc Garry: None declared, D. Veale Grant/research support from: Abbvie,MSD,Pfizer,Roche, Consultant for: Pfizer,Roche, Speakers bureau: Abbott, MSD,Pfzier, Roche, U. Fearon: None declared