中文摘要：

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。

英文摘要：

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.