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.
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.
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.
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.