Gen 对类风湿关节炎 RA 患者 BM-MSCs 中RANK/RANKL/OPG 系统的影响

尚辰, 杨滨州, 张育, 沈维干

尚辰, 杨滨州, 张育, 沈维干. Gen 对类风湿关节炎 RA 患者 BM-MSCs 中RANK/RANKL/OPG 系统的影响[J]. 实用临床医药杂志, 2014, (9): 6-10. DOI: 10.7619/jcmp.201409002
引用本文: 尚辰, 杨滨州, 张育, 沈维干. Gen 对类风湿关节炎 RA 患者 BM-MSCs 中RANK/RANKL/OPG 系统的影响[J]. 实用临床医药杂志, 2014, (9): 6-10. DOI: 10.7619/jcmp.201409002
SHANG Chen, YANG Binzhou, ZHANG Yu, SHEN Weigan. Effect of genistein on the RANK/RANKL/OPG system of BM-MSCs in RA patients[J]. Journal of Clinical Medicine in Practice, 2014, (9): 6-10. DOI: 10.7619/jcmp.201409002
Citation: SHANG Chen, YANG Binzhou, ZHANG Yu, SHEN Weigan. Effect of genistein on the RANK/RANKL/OPG system of BM-MSCs in RA patients[J]. Journal of Clinical Medicine in Practice, 2014, (9): 6-10. DOI: 10.7619/jcmp.201409002

Gen 对类风湿关节炎 RA 患者 BM-MSCs 中RANK/RANKL/OPG 系统的影响

基金项目: 江苏省普通高校研究生科研创新计划项目
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  • 中图分类号: R593

Effect of genistein on the RANK/RANKL/OPG system of BM-MSCs in RA patients

  • 摘要: 目的:研究金雀异黄素(Gen)对类风湿关节炎(RA)患者间充质干细胞(MSCs)中的核因子κB 受体活化因子(RANK)、核因子κB 受体活化因子配体(RANKL)和骨保护素(OPG)系统的影响及其机制。方法分离培养正常人与 RA 患者的骨髓 MSCs(BM-MSCs),分为空白对照组、Gen 处理组、雌二醇(E2)处理组和 Gen +雌激素受体拮抗剂(ICI182780)组,采用 Western blot 法检测 BM-MSCs 中 RANK、RANKL、OPG 的表达;采用免疫荧光法检测雌激素受体α(ERα)细胞内分布情况。结果Western blot 结果显示:与正常人 BM-MSCs 相比,RA 患者 BM-MSCs 中的 RANK 的蛋白表达水平明显升高,OPG 的蛋白表达水平明显降低,RANKL/OPG 比值升高;Gen 显著上调 RA 患者 BM-MSCs 中 OPG 表达,对 RANK、RANKL 表达无明显影响,从而降低了 RANKL/OPG 比值,与 E2作用类似。免疫荧光结果显示:Gen 能促进 RA 患者的 BM-MSCs 中 ERα入核。结论Gen 可能通过活化雌激素受体介导的相关信号通路,调控 RA 患者 BM-MSCs 中 RANKL /OPG 的表达,从而调节破骨细胞分化及成骨细胞分化,抑制 RA 关节破坏和促进受损关节的修复。
    Abstract: Objective To explore the mechanism and effect of genistein (Gen)on receptor activator of nuclear factor kappa B (RANK),RANK ligand (RANKL)and osteoprotegerin (OPG)of mesenchymal stem cells (MSCs)in rheumatoid arthritis (RA)patients.Methods BM-MSCs isolated and cultured from normal adults and RA patients were divided into normal control group,Gen-treated group,E2-treated group and Gen +estrogen receptor antagonist group.Western blot was used to de-tect expression of RANK,RANKL and OPG,and immunofluorescence was used to detect the distribu-tion of estrogen receptorα(ERα)in BM-MSCs.Results According to result of Western blot,com-pared with normal adults,the expression of RANK in BM-MSCs from RA patients was higher,and the expression of OPG was lower,the RANKL/OPG ratio was higher.Similar to E2 treated group,Gen was able to significantly up-regulate the expression of OPG but show no effects on the expression of RANK, RANKL,which resulted in significant decrease of the RANKL/OPG ratio.The results from immunoflu-orescence showed that Gen could facilitate ERαtransferring into the nucleus.Conclusion Gen can regulate the expression and balance of RANKL/OPG in BM-MSCs in RA patients,and further modu-late osteoclast and osteoblast differentiation,inhibit RA joint destruction and promote recovery of dam-aged joints through activating estrogen receptor mediated signal pathway.
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出版历程
  • 发布日期:  2014-07-14

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