Bone and mechanicalstress - TRPV4 channel functions as a mechanosensor -

[目的]TRPV4通道是一种钙离子通透性的阳离子通道，可在中等温度、酸性pH和低渗条件下被激活。TRPV4可作为骨骼上的机械传感器。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和免疫组织化学分析表明，小鼠软骨细胞表达TRPV4。2)电生理分析显示，TRPV4-/-小鼠不存在低张引起的软骨细胞肿胀激活阳离子电流。3)详细的组织学分析显示，TRPV4-/-小鼠软骨细胞分化稍有紊乱。4)骨折愈合模型：TRPV4-/-小鼠与野生型小鼠在组织学上无显著差异。5)原代培养软骨细胞：实时荧光定量聚合酶链式反应分析显示，TRPV4-/-小鼠X型胶原基因的表达模式与野生型小鼠不同。[结论]TRPV4通道可作为机械传感器感知小鼠软骨细胞的低渗状态。TRPV4可能是软骨细胞对机械应力反应的调节机制的组成部分。

[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.