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

• Main Authors: Ping Fan, Lan He, Nan Hu, Jing Luo, Jing Zhang, Ling-Fei Mo, Yan-Hua Wang, Dan Pu, Xiao-Hong Lv, Zhi-Ming Hao, Chang-Hai Ding, Wu-Jun Xue, Yang Li
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2017-05-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Rheumatoid arthritis; 1,25-dihydroxyvitamin D3; MicroRNA-22; Fibroblast-like synoviocytes; Pro-inflammatory cytokine; Collagen induced arthritis
• Online Access: http://www.karger.com/Article/FullText/477123
• ISSN: 1015-8987; 1421-9778

Objective: This study aims to investigate the regulatory mechanism of 1,25-(OH)2D3 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)2D3 the proliferation of FLS was estimated by the MTT method, and the optimal concentration of 1,25-(OH)2D3 was selected for further experiments. Cell proliferation was detected by MTT. Cell cycle and apoptosis were analyzed by FCM. The IL-1β, 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)2D3 and miR-22 inhibitors groups exhibited higher proliferation inhibition and apoptosis rates, lower levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and PGE2), and decreased mRNA expressions 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)2D3 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)2D3 + miR-22 mimics group. Conclusion: Our study demonstrated that 1,25-(OH)2D3 inhibits the proliferation of FLS and alleviates inflammatory response in RA rats by down-regulating miR-22.