Silencing CoREST inhibits the viability and migration of fibroblast‑like synoviocytes in TNF‑α‑induced rheumatoid arthritis

Yu,Ziliang; Chen,Feihu; Liu,Hao; Fan,Jianbo; Ding,Xiaomin; Zhu,Xinhui; Cui,Shengyu; Yi,Hong; Zhou,Xiaogang; Hu,Yalong; Liu,Wei

doi:10.3892/etm.2021.11071

Silencing CoREST inhibits the viability and migration of fibroblast‑like synoviocytes in TNF‑α‑induced rheumatoid arthritis

Authors:
- Ziliang Yu
- Feihu Chen
- Hao Liu
- Jianbo Fan
- Xiaomin Ding
- Xinhui Zhu
- Shengyu Cui
- Hong Yi
- Xiaogang Zhou
- Yalong Hu
- Wei Liu
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Affiliations: Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Orthopaedics, Xuyi People's Hospital, Xuyi, Jiangsu 211700, P.R. China, School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
Published online on: December 15, 2021 https://doi.org/10.3892/etm.2021.11071
Article Number: 148
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Fibroblast‑like synoviocytes (FLSs) have functions in the pathogenesis of rheumatoid arthritis (RA) through the onset of synovitis, the growth of pannus and the destruction of cartilage and bone. The significant increase in the proliferation, migration and invasion of FLSs induces the onset and advancement of RA. To date, the exact function of corepressor element‑1 silencing transcription factor (CoREST) in RA remains unclear, but its expression has been determined in RA synovial tissues. In this study, the effects of CoREST were investigated in a TNF‑α‑induced FLS activation model. Following the silencing of CoREST expression with small interfering (si)RNA, the viability and migration of FLSs were evaluated. Furthermore, the possible molecular mechanisms were explored by detecting the expression of key factors, including matrix metalloproteinases (MMPs), lysine‑specific histone demethylase 1 (LSD1) and associated cytokines, via reverse transcription‑quantitative PCR and western blotting. CoREST expression increased not only in the RA synovial tissues, but also in the TNF‑α‑induced FLS activation model. Following the silencing of CoREST in the FLSs treated with TNF‑α, cell viability was inhibited, and the migratory capacity of FLSs was suppressed, which was accompanied by the reduced expression of MMP‑3 and MMP‑9. The expression of LSD1 was also downregulated. There was a notable decrease in the synthesis of interferon‑γ and interleukin (IL)‑17, while IL‑10 expression was increased. The knockdown of CoREST inhibited the viability and migration of FLSs stimulated with TNF‑α. Thus, the suppression of CoREST may have crucial roles in the occurrence and development of RA.

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