COX2 is involved in hypoxia-induced TNF-α expression in osteoblast.
COX2 is involved in hypoxia-induced TNF-α expression in osteoblast.
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COX2参与缺氧诱导的成骨细胞中TNF-α的表达
DOI：
10.1038/srep10020
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发表时间：
2015-06-12
影响因子：
4.6
通讯作者：
Zhang C
中科院分区：
文献类型：
--
作者：
Xing Y;Wang R;Chen D;Mao J;Shi R;Wu Z;Kang J;Tian W;Zhang C
骨再生以协调的方式涉及一系列事件，包括间充质干细胞的募集、免疫应答的诱导、炎症活性和血管向内生长。骨再生的微环境是缺氧的。低氧张力（缺氧）促进几种信号分子的上调。主要的介导因子是缺氧诱导因子-1（HIF-1）。缺氧刺激炎症细胞、成纤维细胞、内皮细胞和成骨细胞表达多种细胞因子。TNF-α是一种重要的促炎细胞因子。缺氧条件下成骨细胞功能障碍的分子机制尚不完全清楚。本研究旨在探讨缺氧对成骨细胞TNF-α表达的影响及其分子机制。我们观察到缺氧诱导成骨细胞TNF-α表达呈时间依赖性。使用强有力的HIF-1α激活剂DFO的实验表明，低氧诱导的TNF-α是由HIF-1-α介导的。此外，本研究表明，缺氧激活环氧合酶2（COX 2）的表达沿着TNF-α。使用COX 2抑制剂N398的抑制实验表明，COX 2参与缺氧介导的TNF-α表达，并且针对COX 2的小干扰RNA进一步证实了这一观察结果。TNF-α并不激活COX-2的表达。结论COX 2参与了低氧诱导成骨细胞TNF-α的表达。
Bone regeneration involves a series of events in a coordinated manner, including recruitment of mesenchymal stem cells, induction of immune response, inflammatory activity and vascular ingrowth. The microenvironment of bone regeneration is hypoxic. Low oxygen tension (hypoxia) promotes the upregulation of several signaling molecules. The primary mediating factor is the hypoxia-inducible factor-1 (HIF-1). Hypoxia stimulates the expression of a variety of cytokines from inflammatory cells, fibroblasts, endothelial cells, and osteoblasts. TNF-α is a key proinflammatory cytokine. The molecular events involved in osteoblast dysfunction under hypoxia are not fully understood. This study determined the effects of hypoxia on TNF-α in osteoblasts, and molecular mechanisms were explored. We observed that hypoxia induced TNF-α expression in a time-dependent manner in osteoblasts. Experiments using a potent HIF-1α activator DFO demonstrated that hypoxia-induced TNF-α was mediated by HIF-1-α. In addition, this study showed that hypoxia activated cyclooxygenase-2 (COX2) expression along with TNF-α. Inhibition experiments using COX2 inhibitor N398 indicated that COX2 was involved in hypoxia-mediated TNF-α expression, and this observation was further confirmed by Small interfering RNA against COX2. On the other hand, TNF-α didn’t lead to the activation of COX2 expression. We conclude that COX2 is involved in hypoxia-induced TNF-α expression in osteoblast.
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影响因子：
2.7
作者：
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通讯作者：
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