Rosiglitazone inhibits osteoclastogenesis in rheumatoid arthritis by down-regulating RANKL expression and suppressing ERK phosphorylation
10.3969/j.issn.1000-4718.2015.05.025
- VernacularTitle:罗格列酮通过抑制 RANKL 及 p-ERK 活化抑制类风湿关节炎破骨细胞的分化及功能
- Author:
Xiuning WEI
;
Donghui ZHENG
;
Yingqian MO
;
Jianda MA
;
Lie DAI
- Publication Type:Journal Article
- Keywords:
Rheumatoid arthritis;
Fibroblast-like synoviocytes;
Osteoclast;
Receptor activator of nuclear fac-tor-κB ligand;
Peroxisome proliferator-activated receptors γ
- From:
Chinese Journal of Pathophysiology
2015;(5):911-916
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the effects of rosiglitazone on fibroblast-like synoviocyte ( FLS )-induced osteoclastogenesis in rheumatoid arthritis ( RA) and the related mechanism.METHODS: RA-FLS were cocultured with peripheral blood monocytes from healthy volunteers in the presence of macrophage colony-stimulating factor ( M-CSF) and rosiglitazone.Osteoclasts were assayed by tartrate-resistant acid phosphatase ( TRAP) staining.Resorption lacunae area was identified by toluidine blue staining and quantified by image analysis software.The mRNA expression of RANKL and OPG was evaluated by real-time PCR, and the protein levels of RANKL, OPG, p-ERK, p-p38 and p-JNK were measured by Western blot.RESULTS:Compared with control group ( without rosiglitazone treatment) , rosiglitazone at concentration of 15 μmol/L significantly decreased the number of osteoclasts (P<0.01) and resorption lacunae area (P<0.05).The expression of RANKL at mRNA and protein levels was significantly down-regulated by rosiglitazone at concentration of 15μmol/L, while the mRNA and protein expression of OPG was up-regulated (P<0.01).Rosiglitazone (15 μmol/L) sig-nificantly decreased the protein level of p-ERK ( P<0.05 ) , but not the protein level of p-p38 or p-JNK ( P>0.05 ) . CONCLUSION:Rosiglitazone inhibits RA-FLS-induced osteoclast formation and its resorption activity by down-regulating RANKL expression and ERK phosphorylation, suggesting that rosiglitazone may inhibit RA osteoclastogenesis and bone re-sorption.
