PGE2 和 NF-κB信号途径在骨再生中的相互作用
邱小忠, 王国保, 胡晓芳, 王永魁, 张马辉, 王乐禹
中国临床解剖学杂志 ›› 2012, Vol. 30 ›› Issue (3) : 315-319.
PGE2 和 NF-κB信号途径在骨再生中的相互作用
The role of PGE2 and NF-κB pathway during the bone regeneration
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。
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.
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