MicroRNA-101-3p inhibits fibroblast-like synoviocyte proliferation and inflammation in rheumatoid arthritis by targeting PTGS2.

Qiaofeng Wei,Yanhui Cui,Tongying Li,Xinfang Wang,Qin Geng,Yajuan Wang,Shujun Wang,Fang Lv,Hongju Zhang,Xiuying Zhang

doi:10.1042/bsr20191136

Qiaofeng Wei, Yanhui Cui + Show 8 more

Open Access

https://doi.org/10.1042/bsr20191136

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Abstract

Objective: Rheumatoid arthritis (RA) is the most frequently occurring inflammatory arthritis. The present study was performed to characterize the role of microRNA-101-3p (miR-101-3p) and prostaglandin-endoperoxide synthase 2 (PTGS2) in inflammation and biological activities of fibroblast-like synoviocytes (FLSs) in RA.Methods: Initially, miR-101-3p and PTGS2 expression in RA tissues of RA patients and RA rats was detected by qRT-PCR and Western blot analysis. Rat model of type II collagen-induced arthritis (CIA) was adopted to simulate RA, followed by injection of miR-101-3p mimics or siRNA against PTGS2. Next, the apoptosis in synovial tissue and the levels of tumor necrosis factor (TNF)-α, IL-1β and IL-6 were identified. Subsequently, FLSs in RA (RA-FLSs) were isolated, after which in vitro experiments were conducted to analyze cell proliferation, apoptosis, migration and invasion upon treatment of up-regulated miR-101-3p and silenced PTGS2. Furthermore, the relationship of miR-101-3p and PTGS2 was determined by bioinformatics prediction and luciferase activity assay.Results: We identified poorly expressed miR-101-3p and highly expressed PTGS2 in synovial tissues of RA patients and RA rats, which showed reduced synoviocyte apoptosis and enhanced inflammation. In response to miR-101-3p mimics and si-PTGS2, the RA-FLSs were observed with attenuated cell proliferation, migration and invasion, corresponding to promoted apoptosis. Down-regulation of PTGS2 could rescue the effect of inhibited miR-101-3p in synovial injury and phenotypic changes of FLS in RA rats. Notably, miR-101-3p was found to negatively regulate PTGS2.Conclusion: Taken together, miR-101-3p reduces the joint swelling and arthritis index in RA rats by down-regulating PTGS2, as evidenced by inhibited FLS proliferation and inflammation.

Highlights

Rheumatoid arthritis (RA) represents one of the most common chronic joint inflammatory diseases associated with a heavy burden for the patients and the society [1,2]
The results showed that the expression of miR-101-3p in the synovial tissues of RA group was significantly decreased, while the expression of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA and protein elevated, as compared with the normal group (Figure 1C,D), suggesting that miR-101-3p and PTGS2 may be involved in RA occurrence
We further verified the altered expression of miR-101-3p and PTGS2 on the expression of miR-101-3p and PTGS2 in synovial tissues of rats by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot analysis, and we found that expression of miR-101-3p was increased and the expression of PTGS2 decreased in the miR-101-3p mimics group compared with the mimic-negative control (NC) group

Summary

Introduction

Rheumatoid arthritis (RA) represents one of the most common chronic joint inflammatory diseases associated with a heavy burden for the patients and the society [1,2]. In RA, fibroblast-like synoviocytes (FLSs) represent the most common type of cells in cartilage junction, the activation of which stimulates joint destruction by releasing cytokines and chemokines, together with invading and migrating the joint cartilage [9]. No agents have been proved to achieve effective remission in all the RA patients in spite of the advances in treatment, and the toxicities caused by the anti-rheumatic agents inflict the patients [8]. At this point, biomarkers that can serve as therapeutic targets or indicators predicting treatment outcomes are needed.

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