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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

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Fan, P, He, L, Hu, N, Luo, J, Zhang, J, Mo, LF, Wang, YH, Pu, D, Lv, XH, Hao, ZM, Ding, CH ORCID: 0000-0002-9479-730X, Xue, WJ and Li, Y 2017 , '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' , Cellular Physiology and Biochemistry, vol. 42, no. 1 , pp. 145-155 , doi: 10.1159/000477123.

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Abstract

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.

Item Type: Article
Authors/Creators:Fan, P and He, L and Hu, N and Luo, J and Zhang, J and Mo, LF and Wang, YH and Pu, D and Lv, XH and Hao, ZM and Ding, CH and Xue, WJ and Li, Y
Keywords: 1,25-dihydroxyvitamin D3, collagen induced arthritis, fibroblast-like synoviocytes, MicroRNA-22, pro-inflammatory cytokine, rheumatoid arthritis
Journal or Publication Title: Cellular Physiology and Biochemistry
Publisher: Karger
ISSN: 1015-8987
DOI / ID Number: 10.1159/000477123
Copyright Information:

Copyright 2017 The Author(s). Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) http://creativecommons.org/licenses/by-nc-nd/4.0/

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