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首页> 外文期刊>Life sciences >Fas/CD95 is associated with glucocorticoid-induced osteocyte apoptosis
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Fas/CD95 is associated with glucocorticoid-induced osteocyte apoptosis

机译：Fas / CD95与糖皮质激素诱导的骨细胞凋亡相关

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Prolonged use of glucocorticoids is associated with decreased bone formation, increased resorption and osteonecrosis, through direct and indirect effects on the activity and viability of bone effector cells, osteoblasts and osteoclasts, and osteocytes. This study has investigated molecular pathways implicated in Dexamethasone-induced apoptosis of osteocytes, using a cell line and primary chicken cells. MLO-Y4 osteocytes were pre-treated with several bisphosphonates representing a range of anti-resorptive activities and conformation/structure relationships, and were subsequently challenged with Dexamethasone. Apoptotic cells were detected at various times after treatment using morphological and biochemical criteria. Dex was shown to induce apoptosis associated with the Fas/CD95 death receptor and in a caspase 8 dependent manner. The apoptotic response was inhibited by all variants of the BP molecules, including those with reduced anti-resorptive activity, indicating that Dex-induced apoptosis is independent of anti-osteoclastic activity. Dex-induced apoptosis was associated with a transient increase in phosphorylated ERK 1/2 and was blocked by the ERK inhibitor UO126. In addition, both UO126 and BPs decreased localization of Fas to the cell membrane. ERK activation by PMA did not induce death or Fas upregulation, suggesting that Fas may be important for the induction of apoptosis and the existence of an additional factor activated by Dex which enables the cooperation between the Dex-activated ERK and Fas pathways, during apoptosis of osteocytes. Furthermore, upregulation of death and Fas was not accompanied by upregulation of FasL, pointing to the possible existence of FasL-independent Fas-associated death in these cells. (C) 2004 Elsevier Inc.All rights reserved.
机译：长期使用糖皮质激素会通过直接和间接影响骨效应细胞，成骨细胞和破骨细胞以及骨细胞的活性和生存力而减少骨形成，增加吸收和骨坏死。这项研究使用细胞系和原代鸡细胞研究了地塞米松诱导的骨细胞凋亡的分子途径。用代表一系列抗吸收活性和构象/结构关系的双膦酸酯预处理MLO-Y4骨细胞，随后用地塞米松攻击。在处理后的不同时间使用形态学和生化标准检测凋亡细胞。已证明Dex以半胱天冬酶8依赖性方式诱导与Fas / CD95死亡受体相关的凋亡。凋亡反应受到BP分子所有变体的抑制，包括抗吸收活性降低的那些，表明Dex诱导的细胞凋亡与抗破骨细胞活性无关。右旋糖诱导的细胞凋亡与磷酸化ERK 1/2的瞬时增加有关，并被ERK抑制剂UO126阻断。此外，UO126和BP均降低了Fas在细胞膜上的定位。 PMA激活ERK不会引起死亡或Fas上调，提示Fas对于诱导细胞凋亡以及由Dex激活的其他因子的存在可能是重要的，该因子使得Dex激活的ERK和Fas途径之间的协作在细胞凋亡过程中发挥了作用。骨细胞。此外，死亡和Fas的上调并不伴随FasL的上调，这表明这些细胞中可能存在不依赖FasL的Fas相关死亡。 （C）2004 Elsevier Inc.保留所有权利。

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