• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biochemistry >Adenylyl cyclases and TRPV4 mediate Ca2+/ cAMP dynamics to enhance fluid flow-induced osteogenesis in osteocytes
【24h】

Adenylyl cyclases and TRPV4 mediate Ca2+/ cAMP dynamics to enhance fluid flow-induced osteogenesis in osteocytes

机译：腺苷酸环化酶和TRPV4介导Ca2 + / cAMP动力学，以增强骨细胞液流诱导的成骨作用

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Bone adapts to physical forces and this process is dependent on osteocyte mechanotransduction. One way osteocytes sense mechanical stimulation is through the primary cilium, a sensory organelle that triggers intracellular signaling cascades in response to fluid shear. Our lab previously determined that flow-induced ciliary Ca 2+ influx and changes in cytosolic cAMP levels are critical for osteogenesis. We also identified two proteins important for osteocyte mechanotransduction: transient receptor potential vanilloid 4 (TRPV4) and adenylyl cyclase 6 (AC6). Interestingly, disrupting the Ca 2+ -binding ability of these proteins results in loss of function. Although knockdowns of TRPV4 and AC6 disrupt osteogenesis, there is no definitive evidence linking them to Ca 2+ / cAMP dynamics that facilitate osteocyte mechanotransduction. We therefore transfected MLO-Y4 osteocytes with AC3/6 and TRPV4 overexpression plasmids that fail to interact with Ca 2+ and observed the response to fluid shear. Indeed, mutant groups exhibited adverse changes in cAMP and lower mRNA expression of an osteogenic marker, COX-2, at the onset of flow. This pattern persisted for AC3 and TRPV4 but we detected no difference in AC6 at longer exposure to flow. These results suggest TRPV4 and ACs mediate Ca 2+ / cAMP dynamics that are important for osteocyte mechanotransduction. These mechanisms are potential targets for therapeutics to combat bone loss and should be investigated further.
机译：骨骼适应物理力，这个过程依赖于骨细胞机械转导。骨细胞感觉到机械刺激的一种方式是通过初级纤毛，该纤毛是一种感觉细胞器，可响应流体剪切而触发细胞内信号传导级联。我们的实验室先前确定，血流诱发的睫状Ca 2+内流和胞质cAMP水平的变化对于成骨至关重要。我们还确定了两种对骨细胞机械转导重要的蛋白：瞬时受体电位香草酸4（TRPV4）和腺苷酸环化酶6（AC6）。有趣的是，破坏这些蛋白质的Ca 2+结合能力导致功能丧失。尽管敲除TRPV4和AC6会破坏成骨作用，但没有确凿的证据将它们与促进骨细胞机械转导的Ca 2+ / cAMP动态联系起来。因此，我们用AC3 / 6和TRPV4过表达质粒转染了MLO-Y4骨细胞，这些质粒无法与Ca 2+相互作用，并观察到对流体剪切的反应。实际上，突变组在血流开始时表现出cAMP的不利变化和成骨标记物COX-2的较低mRNA表达。对于AC3和TRPV4，这种模式仍然存在，但是在较长的流量下，我们发现AC6没有差异。这些结果表明TRPV4和AC介导Ca 2+ / cAMP动态，这对于骨细胞机械转导很重要。这些机制是对抗骨丢失的疗法的潜在目标，应进一步研究。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号