Physiological and genomic consequences of intermittent hypoxia -: Selected contribution:: Osteocytes upregulate HIF-1α in response to acute disuse and oxygen deprivation
Physiological and genomic consequences of intermittent hypoxia -: Selected contribution:: Osteocytes upregulate HIF-1α in response to acute disuse and oxygen deprivation
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DOI：
10.1152/jappl.2001.90.6.2514
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发表时间：
2001-06-01
影响因子：
3.3
通讯作者：
Mayorov, S
中科院分区：
文献类型：
--
作者：
Gross, TS;Akeno, N;Mayorov, S
机械负荷的丧失或废用会迅速促进局部介导的骨吸收。然而，人们对这一过程的启动和介导途径知之甚少。在这项研究中，我们使用互补的体内和体外方法来确定废弃诱导的骨细胞缺氧是否会导致缺氧依赖性转录因子 HIF-1 α 的上调。我们发现，与正常骨相比，急性废用（1-5 天）导致 HIF-1 α 染色呈阳性的骨细胞百分比显着增加（30.9 +/- 6.1 vs. 14.1 +/- 3.8%），并且这种反应在皮质周围是一致的。此外，我们发现，与正常氧条件下平行培养的细胞相比，急性缺氧（2% O-2 4-12 小时）导致 MLO-Y4 骨细胞样细胞中 HIF-1 α 蛋白表达上调 2.1 至 3.7 倍。鉴于已知的 HIF-1 α 靶基因，我们认为骨细胞缺氧和随后缺氧依赖性途径的上调可能有助于启动和介导废用诱导的骨吸收。
Loss of mechanical loading, or disuse, rapidly precipitates locally mediated bone resorption. However, the pathway by which this process is initiated and mediated is poorly understood. In this study, we used a complementary in vivo and in vitro approach to determine whether disuse-induced osteocyte hypoxia resulted in upregulation of the hypoxia-dependent transcription factor HIF-1 alpha. We found that acute disuse (1-5 days) resulted in a significant increase in the percentage of osteocytes staining positive for HIF-1 alpha vs. normal bone (30.9 +/- 6.1 vs. 14.1 +/- 3.8%) and that this response was uniform around the cortex. In addition, we found that acute oxygen deprivation (4-12 h of 2% O-2) resulted in a 2.1- to 3.7-fold upregulation of HIF-1 alpha protein expression in MLO-Y4 osteocyte-like cells compared with cells cultured in parallel under normal oxygen conditions. Given known HIF-1 alpha targets genes, we suggest that osteocyte hypoxia and subsequent upregulation of hypoxia-dependent pathways may serve to initiate and mediate disuse-induced bone resorption.