HIF-1alpha regulates hypoxia-induced EP1 expression in osteoblastic cells.
HIF-1alpha regulates hypoxia-induced EP1 expression in osteoblastic cells.
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DOI：
10.1002/jcb.22119
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发表时间：
2009-05-15
影响因子：
4
通讯作者：
Yellowley, Clare E.
中科院分区：
文献类型：
--
作者：
Genetos, Damian C.;Lee, Christina M.;Wong, Alice;Yellowley, Clare E.
在骨骼发育和骨折过程中，局部氧张力的变化会刺激局部骨细胞活动，以调节骨骼的形成、维持和修复。骨细胞对低氧的适应性反应才刚刚开始被了解。转录因子HIF-1α在低氧条件下被激活，促进适应和细胞生存所需基因的表达，并调节骨骼发育和骨折修复。我们先前已经证明，缺氧的成骨细胞增加了PGE2的释放和PGE2受体EP1的表达。在目前的研究中，我们研究了HIF-1α活性和表达改变对成骨细胞EP1表达的影响。在21%氧气培养的细胞中，针对phd2的dmog或siRNA可诱导HIF-1α稳定。为了研究缺氧诱导的α在低氧诱导的EP1表达中的作用，我们在缺氧前用针对HIF-1α的小干扰RNA处理成骨细胞。经DMOG或PHD2 siRNA处理后，在21%氧气中培养的细胞EP1的表达明显高于对照组。与对照组相比，HIF-1αsiRNA处理的细胞在低氧条件下的HRE活性降低，表明HIF-1α是该系统中具有功能的HIF-α亚型。此外，经HIF-1EP1siRNA处理的低氧细胞在低氧条件下表现出与对照组相比减少α的表达。抑制SAPK/JNK活性可显著降低缺氧诱导的EP1表达，但对HIF-1α表达或活性无明显影响。这些数据有力地暗示了HIF-1α在低氧诱导的EP1表达中的作用，并可能为HIF-1α调控骨发育和骨折修复的机制提供重要的见解。
Changes in regional oxygen tension that occur during skeletal development and fracture stimulate local bone cell activity to regulate bone formation, maintenance and repair. The adaptive responses of bone cells to hypoxia are only beginning to be understood. The transcription factor HIF-1α is activated under hypoxia and promotes expression of genes required for adaptation and cell survival, and also regulates both bone development and fracture repair. We have previously demonstrated that hypoxic osteoblasts increase PGE2 release and expression of the PGE2 receptor EP1. In the present studies, we investigated the impact of altered HIF-1α activity and expression on EP1 expression in osteoblasts. HIF-1α stabilization was induced in cells cultured in 21% oxygen by treatment with DMOG or siRNA targeted against PHD2. To implicate HIF-1α in hypoxia-induced EP1 expression, osteoblastic cells were treated with siRNA targeted against HIF-1α prior to exposure to hypoxia. EP1 expression was significantly increased in cells cultured in 21% oxygen with DMOG or PHD2 siRNA treatment compared to controls. HRE activation in hypoxia was attenuated in cells treated with HIF-1α siRNA compared to controls, indicating HIF-1α as the functional HIF-α isoform in this system. Furthermore, hypoxic cells treated with HIF-1α siRNA demonstrated reduced EP1 expression in hypoxia compared to controls. Inhibition of SAPK/JNK activity significantly reduced hypoxia-induced EP1 expression but had no impact on HIF-1α expression or activity. These data strongly implicate a role for HIF-1α in hypoxia-induced EP1 expression and may provide important insight into the mechanisms by which HIF-1α regulates bone development and fracture repair.
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影响因子：
2.1
作者：
Caro, J
通讯作者：
Caro, J
DOI：
10.1073/pnas.93.18.9493
发表时间：
1996-09-03
影响因子：
11.1
作者：
Hochachka, PW;Buck, LT;Land, SC
通讯作者：
Land, SC
DOI：
10.1006/bbrc.1998.9151
发表时间：
1998-08-19
影响因子：
3.1
作者：
Matsuda, N;Morita, N;Watanabe, M
通讯作者：
Watanabe, M
影响因子：
4.8
作者：
Conrad, PW;Rust, RT;Beitner-Johnson, D
通讯作者：
Beitner-Johnson, D
影响因子：
56.9
作者：
Bruick, RK;McKnight, SL
通讯作者：
McKnight, SL