首页> 外文期刊>American Journal of Physiology >MAP kinase and calcium signaling mediate fluid flow-induced human mesenchymal stem cell proliferation.
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MAP kinase and calcium signaling mediate fluid flow-induced human mesenchymal stem cell proliferation.

机译:MAP激酶和钙信号传导介导液流诱导人间充质干细胞增殖。

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摘要

Mechanical signals are important regulators of skeletal homeostasis, and strain-induced oscillatory fluid flow is a potent mechanical stimulus. Although the mechanisms by which osteoblasts and osteocytes respond to fluid flow are being elucidated, little is known about the mechanisms by which bone marrow-derived mesenchymal stem cells respond to such stimuli. Here we show that the intracellular signaling cascades activated in human mesenchymal stem cells by fluid flow are similar to those activated in osteoblastic cells. Oscillatory fluid flow inducing shear stresses of 5, 10, and 20 dyn/cm(2) triggered rapid, flow rate-dependent increases in intracellular calcium that pharmacological studies suggest are inositol trisphosphate mediated. The application of fluid flow also induced the phosphorylation of extracellular signal-regulated kinase-1 and -2 as well as the activation of the calcium-sensitive protein phosphatase calcineurin in mesenchymal stem cells. Activation of these signaling pathways combinedto induce a robust increase in cellular proliferation. These data suggest that mechanically induced fluid flow regulates not only osteoblastic behavior but also that of mesenchymal precursors, implying that the observed osteogenic response to mechanical loading may be mediated by alterations in the cellular behavior of multiple members of the osteoblast lineage, perhaps by a common signaling pathway.
机译:机械信号是骨骼动态平衡的重要调节器,应变引起的振荡流体流动是有效的机械刺激。尽管阐明了成骨细胞和成骨细胞响应流体流动的机制,但对于骨髓来源的间充质干细胞响应这种刺激的机制知之甚少。在这里,我们显示在人间充质干细胞中通过流体流动激活的细胞内信号传导级联与在成骨细胞中激活的那些相似。振荡流体流量引起5,10和20 dyn / cm(2)的切应力触发了细胞内钙的快速,流速依赖型增加,药理研究表明这是肌醇三磷酸酯介导的。流体流动的应用还诱导了间充质干细胞中细胞外信号调节激酶-1和-2的磷酸化,以及钙敏感蛋白磷酸酶钙调神经磷酸酶的活化。这些信号传导途径的激活相结合以诱导细胞增殖的强烈增加。这些数据表明,机械诱导的流体流动不仅调节成骨细胞的行为,而且还调节间充质前体的流体,这意味着观察到的对机械负荷的成骨反应可能是由成骨细胞谱系的多个成员的细胞行为的改变介导的,也许是由共同的。信号通路。

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