2. Academic Validation
  3. Triptolide decreases rheumatoid arthritis fibroblast-like synoviocyte proliferation, invasion, inflammation and presents a therapeutic effect in collagen-induced arthritis rats via inactivating lncRNA RP11-83J16.1 mediated URI1 and β-catenin signaling

Triptolide decreases rheumatoid arthritis fibroblast-like synoviocyte proliferation, invasion, inflammation and presents a therapeutic effect in collagen-induced arthritis rats via inactivating lncRNA RP11-83J16.1 mediated URI1 and β-catenin signaling

  • Int Immunopharmacol. 2021 Oct;99:108010. doi: 10.1016/j.intimp.2021.108010.
Xuemei Piao 1,  Jieru Zhou 2,  Luan Xue 3
Affiliations

Affiliations

  • 1 Department of Rheumatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 2 Department of Health Management, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
  • 3 Department of Rheumatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: xelco@163.com.
PMID: 34358861 DOI: 10.1016/j.intimp.2021.108010
Abstract

Objective: Our previous study observed that long non-coding RNA (lncRNA) RP11-83J16.1 promoted rheumatoid arthritis (RA)-fibroblast-like synoviocyte (RA-FLS) proliferation, invasion and inflammation, which was downregulated by triptolide treatment. Therefore, the present study aimed to further investigate the mechanism and interaction between triptolide and lncRNA RP11-83J16.1 in RA treatment in vitro and in vivo.

Methods: RA-FLS was isolated and treated by different concentration of triptolide and lncRNA RP11-83J16.1 overexpression plasmid. Furthermore, collagen-induced arthritis (CIA) rat model was constructed followed by triptolide and lncRNA RP11-83J16.1 overexpression plasmid treatment.

Results: Triptolide inhibited RA-FLS viability and lncRNA RP11-83J16.1 expression in a dose-dependent manner. Afterward, triptolide treatment inhibited RA-FLS proliferation, invasion, levels of inflammatory markers (TNF-α, IL-1β, IL-6, MMP-3, and MMP-9), inactivated lncRNA RP11-83J16.1, URI1 and β-catenin signaling, but promoted Apoptosis. However, lncRNA RP11-83J16.1 overexpression weakened the effects of triptolide on regulating RA-FLS cell behaviors, URI1 signaling and β-catenin signaling. In CIA model, triptolide decreased arthritis score, hyperproliferation of synovial cells, inflammation infiltration of synovial tissue, inflammatory markers (TNF-α, IL-1β, IL-6, MMP-3, and MMP-9), inactivated lncRNA RP11-83J16.1, URI1 and β-catenin signaling, but increased cell Apoptosis rate of synovial tissue. Nevertheless, lncRNA RP11-83J16.1 curtailed the treatment effect of triptolide in CIA model.

Conclusion: Triptolide decreases RA-FLS proliferation, invasion, inflammation and presents a therapeutic effect in CIA model via inactivating lncRNA RP11-83J16.1 mediated URI1 and β-catenin signaling.

Keywords

Fibroblast-like synoviocyte; Inflammation; Long non-coding RNA RP11-83J16.1; Rheumatoid arthritis; Triptolide.

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