Activation of G proteins mediates flow-induced prostaglandin E2 production in osteoblasts.
Activation of G proteins mediates flow-induced prostaglandin E2 production in osteoblasts.
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DOI：
10.1210/endo.138.3.4999
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发表时间：
1997-03
期刊：
影响因子：
4.8
通讯作者：
K. M. Reich;Todd N. McAllister;S. Gudi;J. Frangos
中科院分区：
文献类型：
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作者：
K. M. Reich;Todd N. McAllister;S. Gudi;J. Frangos
间质液流动可能在负荷诱导的骨重塑中起作用。先前，我们已经证明液体流动刺激成骨细胞产生cAMP肌醇三磷酸（IP3）和PGE2。血流诱导的cAMP和IP3的增加是PG产生的结果。因此，PGE2的产生似乎是流体流动诱导信号转导的重要组成部分。在本研究中，我们研究了流动诱导PGE2合成的机理。血流诱导成骨细胞中PGE2的产生增加20倍。在固定细胞中，胍核苷酸结合蛋白（G蛋白）的激活剂ALF4-(10mM)（98倍）和钙离子载体A23187（2微米）（100倍）也观察到增加。然后，我们研究了血流刺激是否由G蛋白介导和细胞内钙的增加。G蛋白抑制剂GDP β S（100微克/毫升）和百日咳毒素（1微克/毫升）对血流诱导的PGE2产生的抑制作用分别为83%和72%。EGTA （2 mM）螯合细胞外钙和quin-2/AM（30微米）螯合细胞内钙分别阻断87%和67%的血流刺激。这些结果表明G蛋白和钙在成骨细胞的机械化学信号转导中起重要作用。
Interstitial fluid flow may play a role in load-induced bone remodeling. Previously, we have shown that fluid flow stimulates osteoblast production of cAMP inositol trisphosphate (IP3), and PGE2. Flow-induced increases in cAMP and IP3 were shown to be a result of PG production. Thus, PGE2 production appears to be an important component in fluid flow induced signal transduction. In the present study, we investigated the mechanism of flow-induced PGE2 synthesis. Flow-induced a 20-fold increase in PGE2 production in osteoblasts. Increases were also observed with ALF4-(10mM) (98-fold), an activator of guanidine nucleotide-binding proteins (G proteins), and calcium ionophore A23187 (2 microM) (100-fold) in stationary cells. We then investigated whether flow stimulation is mediated by G proteins and increases in intracellular calcium. Flow-induced PGE2 production was inhibited by the G protein inhibitors GDP beta S (100 microM) and pertussis toxin (1 microgram/ml) by 83% and 72%, respectively. Chelation of extracellular calcium by EGTA (2 mM) and intracellular calcium by quin-2/AM (30 microM) blocked flow stimulation by 87% and 67%, respectively. These results suggest that G proteins and calcium play an important role in mediating mechanochemical signal transduction in osteoblasts.