Rosiglitazone inhibits receptor activator of NF-κB ligand expression in rheumatoid synovial fibroblasts through p-ERK pathway

Xiuning Wei; Lie Dai; Langjing Zhu; Yingqian MO; Donghui Zheng; Baiyu Zhang

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Rosiglitazone inhibits receptor activator of NF-κB ligand expression in rheumatoid synovial fibroblasts through p-ERK pathway

VernacularTitle:罗格列酮通过p-ERK通路抑制类风湿关节炎滑膜成纤维细胞表达核因子κB受体激活配体
Author: Xiuning WEI ; Lie DAI ; Langjing ZHU ; Yingqian MO ; Donghui ZHENG ; Baiyu ZHANG
Publication Type:Journal Article
Keywords: Arthritis,rheumatoid; Fibroblasts; Receptor activator of uclear factor kappa B ligand; Osteoprotegerin; Rosiglitazone
From: Chinese Journal of Rheumatology 2011;15(9):592-595
CountryChina
Language:Chinese
Abstract: ObjectiveTo investigate the effect of rosiglitazone (RSG), a high-affinity synthetic agonist for PPAR-γ, on the expression of receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG)in rheumatoid arthritis fibroblast-like synoviocyte (RA-FLS) and the underlying mechanisms. MethodsRAFLS were incubated with different concentrations of RSG(0, 5, 10, 15, and 20 μmol/L) for 3 days, RAFLS proliferation was detected by Cell Counting Kit-8 assay, and then the expression of RANKL and OPG was examined by real-time PCR and Western blot. The expression of phosphorylated ERK, p38 and JNK was also detected after RA-FLS was incubated with RSG(0, 15, and 20 μmol/L) for 3 days. One-way ANOVA and Bonferroni were used for statistical analysis. ResultsRSG (5, 10, 15, and 20 μmol/L) had significantly inhibited the expression of RANKL mRNA(0.503±0.005, 0.438±0.031, 0.161±0.042, 0.050±0.018) and protein (1.72±0.09, 1.58x±0.05, 1.46±0.11, 1.22x±0.14) in RA-FLS (F=200.820, F=13.602, P＜0.01 ), while the expression of OPG mRNA (2.8 ±0.5, 7.0 ±3.2, 8.4 ±2.3, 25.7 ±5.1 ) and protein ( 1.21 ±0.11, 1.52 ±0.16, 1.63±0.11, 1.91 ±0.03) increased significantly (F=26.531, F=24.872, P＜0.01), both in a dose dependent manner. The ratio of RANKL/OPG mRNA and protein significantly reduced (F=453.425, P＜0.01 ;F=4.173, P＜0.05 ). RSG (15, 20 μ mol/L) significantly inhibited the expression of p-ERK-1/2 protein (0.55±0.06, 0.45±0.06, F=6.991, P＜0.05). ConclusionRSG can inhibit RANKL expression in RA-FLS through p-ERK pathway.