中国临床解剖学杂志 ›› 2012, Vol. 30 ›› Issue (3): 315-319.

• 实验研究 • 上一篇    下一篇

PGE2 和 NF-κB信号途径在骨再生中的相互作用

邱小忠1, 王国保2, 胡晓芳1, 王永魁1, 张马辉1, 王乐禹1   

  1. 1.南方医科大学人体解剖学教研室, 广东省组织构建与检测重点实验室,  广州   510515;
    2. 南方医科大学南方医院肾内科,  广州   510515
  • 收稿日期:2012-01-30 出版日期:2012-05-25 发布日期:2012-06-06
  • 通讯作者: 王乐禹,女, 博士,讲师, E-mail: wangleyu889@163.com
  • 作者简介:共同第一作者:邱小忠(1968-),男,博士,副教授,研究方向:组织工程E-mail: qqiuxzh@yahoo. com. cn 王国保 (1964-) ,男,副主任医师,副教授,E-mail: wgbandyl @fimmu.com
  • 基金资助:

    广州市科技计划项目(11C32120736)

The role of PGE2 and NF-κB pathway during the bone regeneration

QIU Xiao-zhong1, WANG Guo-bao2,Hu Xiao-fang1,Wang Yong-kui1,Zhang Ma-hui1,Wang Le-yu1   

  1. 1.Institute of Clinical Anatomy, Key Laboratory of Construction and Detection of Guangdong Province, Southern Medical University; 2.Department of Nephrology, Nanfang Hospital Affiliated to Southern Medical University, Guangzhou 510515, China
  • Received:2012-01-30 Online:2012-05-25 Published:2012-06-06

摘要:

目的 本研究旨在利用MC3T3-E1 成骨细胞株与大鼠骨折模型来研究骨折愈合过程中PGE2和NF-κB信号途径的相互作用。  方法 利用PGE2与NF-κB 抑制剂 BAY 11-7082处理MC3T3-E1成骨细胞和大鼠骨折模型,采用碱性磷酸酶活性测定、Western blot 分析、EMSA分析以及ELISA测定等研究手段,研究PGE2、NF-κB、BMP-7、 Id2以及SOD2在骨再生中的作用。  结果 利用10 μmol/l PGE2处理MC3T3-E1细胞10 min, 30 min 和2h后,能够显著地促进成骨细胞增殖与分化,当细胞用5 μmol/L BAY 11-7082处理后,PGE2诱导作用受到抑制,表明 PGE2 增加ALP的表达是通过NF-κB 途径来介导。局部注射NF-κB 抑制剂后 PGE2 的生物合成明显减少;此外,抑制骨折部位ALP的活性,在骨折的损伤修复过程中,NF-κB、BMP-7以及SOD2 的表达均明显上升,而Id2的表达明显下降;加入NF-κB活性抑制剂后,BMP-7与Id2的表达恢复到正常水平,而SOD2的表达没有改变。 结论  PGE2能够同时通过抑制Id2细胞因子和激活NF-κB信号途径诱导成骨细胞分化。

关键词: 骨再生, PGE2, NF-κB

Abstract:

Objective    To study the relationship between the PGE2 production and NF-κB activation in bone regeneration, by combined analysis of the PGE2 production and NF-κB activation in the MC3T3-E1 cells and rat fracture model.   Methods    PGE2 and NF-κB inhibitor BAY 11-708246 were used to deal with MC3T3-E1 cells and rat fracture model. PGE2 production, NF-κB activation and the expression of BMP-7, Id2 and SOD2 were detected during the bone regeneration adopting ALP activity assay, western blot, EMSA analysis and ELISA assay.   Results    After being challenged with 10umol/l PGE2 for 10 min, 30 min and 2h respectively, both of the cell proliferation and differentiation of MC3T3- E1 cells were induced. However, 5umol/l BAY 11-7082 can inhibit the effects of PGE2. This implied that PGE2 induced the expression of ALP through the NF-κB pathway. Local treatment of BAY 11-7082, the production of PGE2 was decreased. On the other hand, Higher NF-κB activation, higher expression of BMP-7and SOD2, and the lower expression of Id2 were appeared in the site of bone fracture. After being injecting of BAY 11-7082, the expression of BMP-7 and Id2 were restored, while the expression of SOD2 was kept unchanged.   Conclusions    PGE2 can inhibit the expression of Id2 and the activation of NF-κB at the same time during the bone regeneration.

Key words: Bone regeneration, PGE2, NF-κB

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