Effect of 1,25-(OH)2D3 on Proliferation of Fibroblast-Like Synoviocytes and Expressions of Pro-Inflammatory Cytokines through Regulating MicroRNA-22 in a Rat Model of Rheumatoid Arthritis

Objective: This study aims to investigate the regulatory mechanism of 1,25-(OH)(2)D-3 on the proliferation of fibroblast-like synoviocytes (FLS) and expressions of pro-inflammatory cytokines in rheumatoid arthritis (RA) rats via microRNA-22 (miR-22). Methods: A rat model of RA was established with a subcutaneous injection of type II collagen. After treated with different concentrations of 1,25-(OH)(2)D-3 the proliferation of FLS was estimated by the MTT method, and the optimal concentration of 1,25-(OH)(2)D-3 was selected for further experiments. Cell proliferation was detected by MTT. Cell cycle and apoptosis wereanalyzed by FCM. The IL-1 beta, IL-6, IL-8, and PGE2 protein expressions were determined by ELISA, and MMP-3, INOS, and Cox-2 mRNA expressions were measured by qRT-PCR. Results: The rat model of RA was successfully established. Compared with the blank group, the 1,25-(OH)(2)D-3 and miR-22 inhibitors groups exhibited higher proliferation inhibition and apoptosis rates, lower levels of pro-inflammatory cytokines (IL-1 beta, IL-6, IL-8, and PGE2), and decreased mRNAexpressions of MMP-3, INOS, and Cox-2. The miR-22 mimics group had lower proliferation inhibition and apoptosis rates, elevated expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 than the blank group. In contrast to the 1,25-(OH)(2)D-3 group, the proliferation inhibition and apoptosis rates were down-regulated, and the expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 were up-regulated in the 1,25-(OH)(2)D-3 + miR-22 mimics group. Conclusion: Our study demonstrated that 1,25-(OH)(2)D-3 inhibits the proliferation of FLS and alleviates inflammatory response in RA rats by down-regulating miR-22. (C) 2017 The Author(s) Published by S. Karger AG, Basel