Study on the role of small G proteins in mechanotransduction

机械刺激是维持骨稳态的重要因素。阐明机械刺激导致骨形成的信号传导途径（mechanotransduction pathway）是非常重要的。在本研究中，我们使用药理学方法研究了Rho在机械转导中的作用，Rho是一种调节细胞结构的小G蛋白。我们开发了一种改进的加载设备，能够以毫牛顿分辨率和微米位移向有活力的骨移植体提供载荷，并确定了最大合成代谢响应的加载条件。利用组织培养系统和微力学测试装置进行药理学研究Rho家族的小G蛋白可能在导致骨形成的机械转导途径中起负调节作用。利用细胞培养系统和Flexercell菌株进行的药理学研究表明，Rho家族的小G蛋白参与了成骨细胞产生一氧化氮的过程。然而，它们是否在成骨细胞循环张力刺激的信号转导中起作用尚不清楚。未来展望尽管目前的研究结果表明Rho家族的小G蛋白参与了骨的机械转导途径，但它们的作用尚不清楚，其他小G蛋白家族的作用尚不清楚。这些问题需要进一步的分子生物学和药理学研究来解决。

Mechanical stimulus is an essential factor for the maintenance of bone homeostasis. It is important to clarify the signal transduction pathway of mechanical stimulation (mechanotransduction pathway) leading to bone formation. In the present study, we investigated the role of Rho, a small G protein that regulates cellular configuration, in the mechanotransduction using pharmacological approach.1.Development of a micromechanical testing device and establishment of the assay systemWe developed an improved loading device capable of delivering loads with milli-Newton resolution and micrometer displacements to viable bone explants and determined conditions of loading which give the maximum anabolic responses.2.Pharmacological study using a tissue culture system and the micromechanical testing deviceIt was suggested that small G proteins of Rho family might act as a negative regulator in the mechanotransduction pathway that leads to bone formation.3.Pharmacological study using a cell culture system and the Flexercell Strain UnitIt was suggested that small G proteins of Rho family are involved in the nitric oxide production by osteoblasts. However, it is not known whether they have any role in the signal transduction of a cyclic tensional stimulus in osteoblastic cells.4.Future prospectAlthough the present results suggest that small G proteins of Rho family, are involved in the mechanotransduction pathway in bone, their role remains unclear and roles of the other families of small G proteins are not known. Further studies using molecular biological approach as well as pharmacological approach would be required to solve these questions.