Bone and mechanicalstress - TRPV4 channel functions as a mechanosensor -

骨骼和机械应力 - TRPV4 通道充当机械传感器 -

• 批准号: 17590255
• 负责人: MIZUNO Atsuko
• 金额: $ 2.24万
• 依托单位: Jichi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590255/
• 关键词: cell tissue; regenerative medicine; biologic molecule

[Objective]TRPV4 channel is a calcium permeable cation channel which is activated by moderate heat, acidic pH and hypotonicity. TRPV4 may play as a mechanosensor on bone. To test this possibility, we compared the bone mass and chondrocytes, in TRPV4-/- mice and wild-type mice.[Results]1) RT-PCR and immunohistochemical analysis showed that mouse chondrocytes express TRPV4. 2) Electrophysiologic analysis revealed that the swell-activated cation current on chondrocyte induced by hypotonicity was absent in TRPV4-/- mice. 3) Detailed histological analysis showed that differentiation of chondrocytes in TRPV4-/- mice was slightly disordered. 4) Fracture healing model : there were no significant histological differences between TRPV4-/- and wild-type mice. 5) Primary cultured chondrocytes: expression patterns of collagen type X mRNA in TRPV4-/- mice were different from those in wild-type mice, by real-time PCR analysis.[Conclusion]TRPV4 channel functions as a mechanosensor sensing hypotonicity on the chondrocytes in mice. TRPV4 may act as a component molecule of the regulatory mechanism to response to mechanical stress in chondrocytes.

【目的】TRPV4通道是一种中热、酸性pH和低渗激活的钙渗透阳离子通道。TRPV4可作为骨上的机械传感器。为了验证这种可能性，我们比较了TRPV4-/-小鼠和野生型小鼠的骨量和软骨细胞。【结果】1)RT-PCR和免疫组化分析显示，小鼠软骨细胞表达TRPV4。2)电生理分析显示，TRPV4-/-小鼠低张力诱导的软骨细胞肿胀激活的阳离子电流不存在。3)详细的组织学分析显示，TRPV4-/-小鼠软骨细胞分化有轻微紊乱。4)骨折愈合模型：TRPV4-/-与野生型小鼠无明显组织学差异。5)原代培养软骨细胞：通过实时荧光定量PCR分析，TRPV4-/-小鼠与野生型小鼠胶原X型mRNA的表达模式不同。【结论】TRPV4通道对小鼠软骨细胞的低张力具有机械传感器的作用。TRPV4可能作为软骨细胞对机械应力响应调控机制的组成分子。