PGE2抑制肿瘤坏死因子诱导的成骨细胞凋亡  

Prostaglandin E2 Inhibits TNFα-induced Apoptosis in Mouse Osteoblasts

作　　者：杨周岐[1] 孟芮[1] 王哲[1] 张维[1] 商澎[1] 

机构地区：[1]空间生物实验模拟技术重点实验室西北工业大学生命学院特殊环境生物物理学研究所,西安710072

出　　处：《中国细胞生物学学报》2011年第1期27-34,共8页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(No.30970689)资助项目~~

摘　　要：前列腺素E2(PGE2)通过自分泌或旁分泌方式调节成骨细胞的增殖和分化。本文以小鼠原代成骨细胞和成骨样细胞MC3T3-E1为实验材料,研究了PGE2对肿瘤坏死因子α(TNF-α)诱导的成骨细胞凋亡的调节作用。检测发现,振荡型流体剪切力(OFSS)刺激可诱导成骨细胞内环氧合酶2(COX-2)表达升高,进而促进PGE2合成,并抑制TNF-α诱导的成骨细胞凋亡。COX-2选择性活性抑制剂NS-398显著促进TNF-α诱导的成骨细胞内半胱天冬酶3(caspase-3)的激活,且呈时间依赖性。Hoechst 33258/PI染色检测发现,NS-398促使TNF-α诱导的成骨细胞膜通透性进一步增强,核染色质浓缩加剧,而PGE2可显著抑制这一效应。Caspase-3活性检测证实,NS-398显著促进TNF-α诱导的成骨细胞内caspase-3活性增强,外源性PGE2可有效对抗该效应。这些结果表明,内源性和外源性PGE2可抑制TNF-α诱导的成骨细胞凋亡发生。Previous studies have revealed that prostaglandin E2（PGE2） regulated the proliferation and differentiation of osteoblasts in the manner of autocrine or paracrine.In this study,the regulatory role of PGE2 on TNFα-induced apoptosis in primary mouse osteoblasts or osteoblast-like MC3T3-E1 cells was investigated.The results demonstrated that oscillatory fluid shear stress（OFSS） promoted the expression of cyclooxygenase-2（COX- 2）,stimulated PGE2 secretion in culture media,and inhibited TNFα-induced apoptosis in primary osteoblasts and MC3T3-E1 cells.Application of COX-2 selective inhibitor NS-398 significanly enhanced TNFoc-induced activation of caspase-3 in osteoblasts in a time-dependent manner.Hoechst 33258/PI staining experiment showed that NS-398 distinctly increased the membrane permeability and the chromatin condensation in osteoblasts,however,application of PGE2 suppressed this effect.Further investigation indicated that NS-398 increased the activity of caspase-3 induced by TNF-αin osteoblasts,and the addition of exogenous PGE2 in culture media restrained this effect.In conclusion,endogenous and exogenous PGE2 inhibits TNFα-induced apoptosis in mouse osteoblasts.

关 键 词：前列腺素E2 成骨细胞 凋亡 肿瘤坏死因子-α 

分 类 号：R346[医药卫生—基础医学]