Steady and transient fluid shear stress stimulate NO release in osteoblasts through distinct biochemical pathways
Steady and transient fluid shear stress stimulate NO release in osteoblasts through distinct biochemical pathways
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DOI：
10.1359/jbmr.1999.14.6.930
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发表时间：
1999-06-01
影响因子：
6.2
通讯作者：
Frangos, JA
中科院分区：
文献类型：
--
作者：
McAllister, TN;Frangos, JA
流体现在已被证明是成骨细胞和骨细胞的一种强有力的刺激，因此可能在负荷诱导的骨重建中发挥重要作用。本研究的目的是探讨流动激活的途径的特点。以前，我们报道，流体现在刺激快速和连续释放一氧化氮（NO）在原代大鼠颅骨成骨细胞，我们证明，现在诱导的NO释放是由剪切应力介导的，这种反应是明显的双相。瞬时的剪切应力与现在的发作刺激NO产生的爆发（8.2 nmol/mg蛋白/h），而稳定流刺激持续的NO生产（2.2 nmol/mg蛋白/h）。G-蛋白抑制和钙螯合消除爆发阶段，但对持续生产没有影响。G蛋白的激活刺激了静态培养的颅骨成骨细胞和UMR-106成骨细胞样细胞中的剂量依赖性NO释放。百日咳毒素对NO释放无影响。钙离子载体在15分钟内刺激低水平的NO产生，但对持续产生没有影响。两者合计，这些数据表明，流体剪切应力刺激NO释放两个不同的途径：G-蛋白和钙依赖性相敏感的流量瞬变，和G-蛋白和钙独立的途径刺激持续流。
Fluid now has been shown to be a potent stimulus in osteoblasts and osteocytes and may therefore play an important role in load-induced bone remodeling. The objective of this study was to investigate the characteristics of flow-activated pathways. Previously we reported that fluid now stimulates rapid and continuous release of nitric oxide (NO) in primary rat calvarial osteoblasts, Were we demonstrate that now-induced NO release is mediated by shear stress and that this response is distinctly biphasic. Transients in shear stress associated with the onset of now stimulated a burst in NO production (8.2 nmol/mg of protein/h), while Steady flow stimulated sustained NO production (2.2 nmol/mg of protein/h), Both G-protein inhibition and calcium chelation abolished the burst phase but had no effect on sustained production. Activation of G-proteins stimulated dose-dependent NO release in static cultures of both,calvarial osteoblasts and UMR-106 osteoblast-like cells. Pertussis toxin had no effect on NO release. Calcium ionophore stimulated low levels of NO production within 15 minutes but had no effect on sustained production. Taken together, these data suggest that fluid shear stress stimulates NO release by two distinct pathways: a G-protein and calcium-dependent phase sensitive to flow transients, and a G-protein and calcium-independent pathway stimulated by sustained flow.