中国病理生理杂志
中國病理生理雜誌
중국병리생리잡지
CHINESE JOURNAL OF PATHOPHYSIOLOGY
2015年
5期
911-916
,共6页
韦秀宁%郑东辉%莫颖倩%马剑达%戴冽
韋秀寧%鄭東輝%莫穎倩%馬劍達%戴冽
위수저%정동휘%막영천%마검체%대렬
类风湿关节炎%成纤维样滑膜细胞%破骨细胞%核因子κB受体活化因子配体%过氧化物酶体增殖物活化受体γ
類風濕關節炎%成纖維樣滑膜細胞%破骨細胞%覈因子κB受體活化因子配體%過氧化物酶體增殖物活化受體γ
류풍습관절염%성섬유양활막세포%파골세포%핵인자κB수체활화인자배체%과양화물매체증식물활화수체γ
Rheumatoid arthritis%Fibroblast-like synoviocytes%Osteoclast%Receptor activator of nuclear fac-tor-κB ligand%Peroxisome proliferator-activated receptors γ
目的：探讨罗格列酮（RSG）对类风湿关节炎（RA）成纤维样滑膜细胞（FLS）介导的破骨细胞（Oc）分化及功能的影响及其可能机制。方法：活动期RA患者滑膜体外分离培养FLS，与健康人外周血单核细胞（MNC）共培养，不同浓度RSG （0、5、10和15μmol／L）干预，抗酒石酸酸性磷酸酶（TRAP）染色鉴定Oc并计数；甲苯胺蓝染色和图像分析系统计算骨吸收陷窝面积；Real-time PCR检测共培养体系RANKL和OPG的mRNA表达， Western blot检测RANKL、OPG、p-ERK、p-p38和p-JNK的蛋白含量。结果：与不加RSG组比较，15μmol／L RSG干预后Oc的数量明显减少（P＜0.01），骨吸收陷窝面积也减少（P＜0.05）；共培养体系RANKL的mRNA及蛋白表达明显降低，OPG的mRNA及蛋白表达明显升高（P＜0.01）；p-ERK的蛋白含量明显降低（P＜0.05），p-p38及p-JNK的蛋白含量则不受影响。结论：RSG通过抑制RANKL及p-ERK活化影响RA关节微环境中组织细胞与免疫细胞的相互作用，从而抑制Oc分化及骨吸收功能。
目的：探討囉格列酮（RSG）對類風濕關節炎（RA）成纖維樣滑膜細胞（FLS）介導的破骨細胞（Oc）分化及功能的影響及其可能機製。方法：活動期RA患者滑膜體外分離培養FLS，與健康人外週血單覈細胞（MNC）共培養，不同濃度RSG （0、5、10和15μmol／L）榦預，抗酒石痠痠性燐痠酶（TRAP）染色鑒定Oc併計數；甲苯胺藍染色和圖像分析繫統計算骨吸收陷窩麵積；Real-time PCR檢測共培養體繫RANKL和OPG的mRNA錶達， Western blot檢測RANKL、OPG、p-ERK、p-p38和p-JNK的蛋白含量。結果：與不加RSG組比較，15μmol／L RSG榦預後Oc的數量明顯減少（P＜0.01），骨吸收陷窩麵積也減少（P＜0.05）；共培養體繫RANKL的mRNA及蛋白錶達明顯降低，OPG的mRNA及蛋白錶達明顯升高（P＜0.01）；p-ERK的蛋白含量明顯降低（P＜0.05），p-p38及p-JNK的蛋白含量則不受影響。結論：RSG通過抑製RANKL及p-ERK活化影響RA關節微環境中組織細胞與免疫細胞的相互作用，從而抑製Oc分化及骨吸收功能。
목적：탐토라격렬동（RSG）대류풍습관절염（RA）성섬유양활막세포（FLS）개도적파골세포（Oc）분화급공능적영향급기가능궤제。방법：활동기RA환자활막체외분리배양FLS，여건강인외주혈단핵세포（MNC）공배양，불동농도RSG （0、5、10화15μmol／L）간예，항주석산산성린산매（TRAP）염색감정Oc병계수；갑분알람염색화도상분석계통계산골흡수함와면적；Real-time PCR검측공배양체계RANKL화OPG적mRNA표체， Western blot검측RANKL、OPG、p-ERK、p-p38화p-JNK적단백함량。결과：여불가RSG조비교，15μmol／L RSG간예후Oc적수량명현감소（P＜0.01），골흡수함와면적야감소（P＜0.05）；공배양체계RANKL적mRNA급단백표체명현강저，OPG적mRNA급단백표체명현승고（P＜0.01）；p-ERK적단백함량명현강저（P＜0.05），p-p38급p-JNK적단백함량칙불수영향。결론：RSG통과억제RANKL급p-ERK활화영향RA관절미배경중조직세포여면역세포적상호작용，종이억제Oc분화급골흡수공능。
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.
