Inhibition of osteocyte apoptosis by fluid flow is mediated by nitric oxide
Inhibition of osteocyte apoptosis by fluid flow is mediated by nitric oxide
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DOI：
10.1016/j.bbrc.2008.03.007
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发表时间：
2008-05-16
影响因子：
3.1
通讯作者：
Klein-Nulend, J.
中科院分区：
文献类型：
--
作者：
Tan, S. D.;Bakker, A. D.;Klein-Nulend, J.
骨卸载导致骨细胞凋亡，从而吸引破骨细胞导致骨质流失。骨的负载驱动液体流过骨细胞，骨细胞通过释放信号分子（如一氧化氮（NO））做出反应，抑制骨细胞凋亡并改变成骨细胞和破骨细胞活性，从而防止骨质流失。然而，哪些凋亡相关基因受负载调节尚不清楚。我们研究了骨细胞、成骨细胞和成纤维细胞中脉动流体流 (PFF) 响应的凋亡相关基因表达，以及这是否是由负荷诱导的 NO 产生介导的。 PEE（0.7 +/- 0.3 Pa，5 Hz，1 h）上调骨细胞中的 Bcl-2 和 caspase-3 表达。 L-NAME 减弱了这种效应。在骨细胞中，PFF 不影响 p53 和 c-Jun，但 L-NAME 上调 c-Jun 表达。在成骨细胞和成纤维细胞中，PFF 上调 c-Jun 表达，但不上调 Elcl-2、caspase-3 和 p53 表达。这表明 PFF 通过改变 Bcl-2 和 caspase-3 基因表达来抑制骨细胞凋亡，而 Bcl-2 和 caspase-3 基因表达至少部分受 NO 调节。 (C) 2008 Elsevier Inc. 保留所有权利。
Bone unloading results in osteocyte apoptosis, which attracts osteoclasts leading to bone loss. Loading of bone drives fluid flow over osteocytes which respond by releasing signaling molecules, like nitric oxide (NO), that inhibit osteocyte apoptosis and alter osteoblast and osteoclast activity thereby preventing bone loss. However, which apoptosis-related genes are modulated by loading is unknown. We studied apoptosis-related gene expression in response to pulsating fluid flow (PFF) in osteocytes, osteoblasts, and fibroblasts, and whether this is mediated by loading-induced NO production. PEE (0.7 +/- 0.3 Pa, 5 Hz, 1 h) upregulated Bcl-2 and clownregulated caspase-3 expression in osteocytes. L-NAME attenuated this effect. In osteocytes PFF did not affect p53 and c-Jun, but L-NAME upregulated c-Jun expression. In osteoblasts and fibroblasts PFF upregulated c-Jun, but not Elcl-2, caspase-3, and p53 expression. This suggests that PFF inhibits osteocyte apoptosis via alterations in Bcl-2 and caspase-3 gene expression, which is at least partially regulated by NO. (C) 2008 Elsevier Inc. All rights reserved.