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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。
Prostaglandin E2 (PGE2) regulates the proliferation and differentiation of osteoblasts through autocrine or paracrine processes. In this study, primary cultured mouse osteoblasts and osteoblastic MC3T3-E1 cells were used as experimental materials to study the regulatory effect of PGE2 on osteoblast apoptosis induced by tumor necrosis factor-α (TNF-α). It was found that oscillating fluid shear stress (OFSS) stimulated the expression of cyclooxygenase 2 (COX-2) in osteoblasts, and then promoted the synthesis of PGE2 and inhibited the apoptosis of osteoblasts induced by TNF-α . NS-398, a selective inhibitor of COX-2, significantly promoted TNF-α-induced caspase-3 activation in a time-dependent manner. Hoechst 33258 / PI staining showed that NS-398 enhanced TNF-α-induced osteoblast membrane permeability and enhanced chromatin condensation, while PGE2 significantly inhibited this effect. Caspase-3 activity test confirmed that NS-398 significantly enhanced the activity of caspase-3 induced by TNF-α in osteoblasts, and exogenous PGE2 could effectively counteract this effect. These results indicate that endogenous and exogenous PGE2 can inhibit TNF-α-induced apoptosis of osteoblasts.