首页> 外文期刊>Pathobiology: journal of immunopathology, molecular and cellular biology >Altered expression of apoptosis-related genes in osteocytes exposed to high-dose steroid hormones and hypoxic stress.
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Altered expression of apoptosis-related genes in osteocytes exposed to high-dose steroid hormones and hypoxic stress.

机译:暴露于高剂量类固醇激素和低氧应激的骨细胞中凋亡相关基因的表达变化。

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OBJECTIVE: High-dose steroid hormones cause necrosis of the femoral head. Since steroid hormones function as blood coagulants, we hypothesized that ischemic hypoxia induced by steroid hormones is critical for apoptosis which occurs before necrosis of osteocytes. METHODS: We performed an analysis of gene expression in the process of leading osteocytes to apoptosis, using a mouse cell line. Cultured osteocytes were loaded with hypoxic stress with or without exposure to steroid hormones, and the gene expression under these conditions was investigated using a cDNA array and real-time quantitative RT-PCR. RESULTS: The proapoptotic p53 gene was downregulated under a hypoxic (1% O2) condition without exposure to steroid hormones. On the other hand, the expression of antiapoptotic Bcl-2 gene was increased by exposure to high-dose steroid hormones under a normoxic condition (20% O2). Interestingly, both proapoptotic (p53 and Bax) and antiapoptotic (Bcl-2 and MDM2)genes were downregulated in osteocytes treated with high-dose steroid hormones in the hypoxic environment. CONCLUSIONS: These findings suggest that osteocytes exposed to high-dose steroid hormones appear to be more sensitive to apoptosis in the hypoxic environment than those without exposure to steroid hormones. This concept helps to understand the pathogenesis of idiopathic necrosis of the bone.
机译:目的:大剂量类固醇激素会导致股骨头坏死。由于类固醇激素起着凝血剂的作用,我们假设类固醇激素引起的缺血性缺氧对于在骨细胞坏死之前发生的细胞凋亡至关重要。方法:我们使用小鼠细胞系对导致骨细胞凋亡的过程中的基因表达进行了分析。在有或没有暴露于类固醇激素的情况下,对培养的骨细胞施加低氧应激,并使用cDNA阵列和实时定量RT-PCR研究了在这些条件下的基因表达。结果:在缺氧(1%O2)条件下,未暴露于类固醇激素的情况下,促凋亡的p53基因被下调。另一方面,通过在常氧条件下(20%O2)暴露于高剂量类固醇激素,抗凋亡Bcl-2基因的表达增加。有趣的是,在低氧环境中,用高剂量类固醇激素治疗的骨细胞中的促凋亡基因(p53和Bax)和抗凋亡基因(Bcl-2和MDM2)均被下调。结论:这些发现表明,在低氧环境中暴露于高剂量类固醇激素的骨细胞比未暴露于类固醇激素的骨细胞似乎对细胞凋亡更为敏感。这个概念有助于了解骨特发性坏死的发病机理。

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