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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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posted on 2023-05-19, 16:34 authored by Fan, P, He, L, Hu, N, Luo, J, Zhang, J, Mo, LF, Wang, YH, Pu, D, Lv, XH, Hao, ZM, Chang-Hai DingChang-Hai Ding, Xue, WJ, Li, Y
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.

History

Publication title

Cellular Physiology and Biochemistry

Volume

42

Pagination

145-155

ISSN

1015-8987

Department/School

Menzies Institute for Medical Research

Publisher

Karger

Place of publication

Allschwilerstrasse 10, Basel, Switzerland, Ch-4009

Rights statement

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/

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified

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