Hypoxic stress enhances osteoclast differentiation via increasing IGF2 production by non-osteoclastic cells
Hypoxic stress enhances osteoclast differentiation via increasing IGF2 production by non-osteoclastic cells
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DOI：
10.1016/j.bbrc.2005.01.042
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发表时间：
2005-03-25
影响因子：
3.1
通讯作者：
Goto, S
中科院分区：
文献类型：
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作者：
Fukuoka, H;Aoyama, M;Goto, S
骨的发育依赖于骨降解破骨细胞的持续供应。虽然细胞因子和整合素等因素已被证明对破骨细胞募集很重要，但它们的作用机制尚不清楚。在这项研究中，我们证明了缺氧对破骨细胞形成的促进作用，并研究了其中的分子机制。在常氧和缺氧条件下培养小鼠原代骨髓细胞，从每组细胞中制备RNA。将总rna应用于DNA芯片分析，然后进行RT-PCR验证芯片数据。我们的微阵列分析最有趣的发现是在缺氧条件下胰岛素样生长因子2 （IGF2）和基质细胞衍生因子I （SDF1）的上调。RT-PCR分析显示，IGF2在非破骨细胞中表达明显上调。外源性IGF2的添加增加了在常温条件下形成的破骨细胞trap阳性多核细胞的数量，而外源性SDF1的添加没有改变破骨细胞的形成。这些结果表明，来自非破骨细胞的IGF2的上调可能是破骨细胞分化的关键因素。(C) 2005爱思唯尔公司版权所有。
Development of bone depends on a continuous supply of bone-degrading osteoclasts. Although several factors such as cytokines and integrins have been shown to be important for osteoclast recruitment, their mechanism of action is poorly understood. In this study, we demonstrated the enhancement of osteoclast formation by hypoxia and investigated the molecular mechanisms involved. Primary mouse bone marrow cells were cultured in normoxic and hypoxic conditions, and RNA was prepared from each group of cells. Total RNAs were applied to a DNA microarray analysis and then RT-PCR was performed to confirm the microarray data. The most interesting finding of our microarray analysis was upregulation of insulin-like growth factor 2 (IGF2) and stromal cell-derived factor I (SDF1) under hypoxic conditions. RT-PCR analysis revealed that IGF2 expression was markedly upregulated in the non-osteoclastic cells. The addition of exogerious IGF2 increased the number of osteoclastic TRAP-positive multinuclear cells formed under normoxic conditions, whereas the addition of exogenous SDF1 did not change osteoclast formation. These results suggest that the upregulation of IGF2 derived from non-osteoclastic cells might be a crucial factor for osteoclast differentiation. (C) 2005 Elsevier Inc. All rights reserved.