Brief Reports: TRPM7 Senses Mechanical Stimulation Inducing Osteogenesis in Human Bone Marrow Mesenchymal Stem Cells
Brief Reports: TRPM7 Senses Mechanical Stimulation Inducing Osteogenesis in Human Bone Marrow Mesenchymal Stem Cells
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简要报告：TRPM7 感知机械刺激诱导人骨髓间充质成骨
DOI：
10.1002/stem.1858
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发表时间：
2015-02-01
期刊：
影响因子：
5.2
通讯作者：
Zhang, Yi
中科院分区：
文献类型：
--
作者：
Xiao, E.;Yang, H. Q.;Zhang, Yi
间充质干细胞（MSC）是存在于骨髓中的多能干细胞。多项研究表明，机械刺激通过第二信使的动员来调节 MSC 分化，但机械转导的机制仍知之甚少。在这项研究中，利用荧光和激光共聚焦显微镜以及膜片钳技术，我们确定了瞬态受体电位褪黑素7型（TRPM7）通道是参与骨髓间充质干细胞机械转导的关键通道。 TRPM7 敲低完全消除了压力诱导的胞质 Ca2+ 增加和压力诱导的成骨作用。 TRPM7 直接感知膜张力，独立于细胞质和细胞骨架的完整性。 Ca2+ 通过 TRPM7 流入进一步触发内质网上肌醇三磷酸受体 2 型释放 Ca2+，并促进 NFATc1 核定位和成骨。这些结果确定了 TRPM7 在 MSC 机械刺激诱导的成骨中的核心作用。
Mesenchymal stem cells (MSCs) are multipotential stem cells residing in the bone marrow. Several studies have shown that mechanical stimulation modulates MSC differentiation through mobilization of second messengers, but the mechanism of mechanotransduction remains poorly understood. In this study, using fluorescence and laser confocal microcopy as well as patch-clamp techniques, we identified the transient receptor potential melastatin type 7 (TRPM7) channel as the key channel involved in mechanotransduction in bone marrow MSCs. TRPM7 knockdown completely abolished the pressure-induced cytosolic Ca2+ increase and pressure-induced osteogenesis. TRPM7 directly sensed membrane tension, independent of the cytoplasm and the integrity of cytoskeleton. Ca2+ influx through TRPM7 further triggered Ca2+ release from the inositol trisphosphate receptor type 2 on the endoplasmic reticulum and promoted NFATc1 nuclear localization and osteogenesis. These results identified a central role of TRPM7 in MSC mechanical stimulation-induced osteogenesis.