Xiao E, Yang H Q, Gan Ye-Hua, Duan Deng-Hui, He Lin-Hai, Guo YunBo, Wang S Q, Zhang Yi
Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, People's Republic of China.
Stem Cells. 2015 Feb;33(2):615-21. doi: 10.1002/stem.1858.
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 Ca(2+) increase and pressure-induced osteogenesis. TRPM7 directly sensed membrane tension, independent of the cytoplasm and the integrity of cytoskeleton. Ca(2+) influx through TRPM7 further triggered Ca(2+) 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.
间充质干细胞（MSCs）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的分化，但机械转导的机制仍知之甚少。在本研究中，我们使用荧光和激光共聚焦显微镜以及膜片钳技术，确定瞬时受体电位香草素7型（TRPM7）通道是骨髓间充质干细胞机械转导的关键通道。TRPM7基因敲低完全消除了压力诱导的胞质Ca(2+)增加和压力诱导的成骨作用。TRPM7直接感知膜张力，与细胞质和细胞骨架的完整性无关。通过TRPM7的Ca(2+)内流进一步触发内质网上2型三磷酸肌醇受体释放Ca(2+)，并促进NFATc1核定位和成骨作用。这些结果确定了TRPM7在MSC机械刺激诱导成骨中的核心作用。
