Amelioration of Experimental Autoimmune Arthritis Through Targeting of Synovial Fibroblasts by Intraarticular Delivery of MicroRNAs 140-3p and 140-5p.

摘要: OBJECTIVE Synovial fibroblasts (SFs) with aberrant expression of microRNAs (miRNAs) are critical pathogenic regulators in rheumatoid arthritis (RA), and studies analyzing the effect overexpressing or silencing miRNA models can contribute to development miRNA-based therapeutic strategies. This study was undertaken examine hypothesis that miRNAs 140-3p 140-5p involved pathogenesis RA, determine whether targeting SFs through intraarticular (IA) delivery these molecules could ameliorate autoimmune mice. METHODS tissue samples were obtained from patients RA. In addition, 2 experimental mice used, collagen-induced (CIA) collagen antibody-induced (CAIA). Overexpression synovial induced using lentivirus (LV)-mediated transfer pre-miR-140 precursor molecules. RESULTS Lower levels miR-140-3p miR-140-5p detected RA both models. CIA CAIA, LV-mediated IA ameliorated arthritis, as determined by clinical examination histopathologic evaluations showing a decrease SF densities. caused reduction expression, correlated kinetic patterns, their corresponding target sirtuin 1 stromal cell-derived factor joints Transfection into increased cell apoptosis, reduced proliferation responses migration abilities, verified concept miR-140 is regulated proinflammatory cytokines. CONCLUSION These results demonstrate arthritis. findings might facilitate pharmacologic molecular-based therapies