MECHANOTRANSDUCTION IN BONE VIA OSCILLATING FLUID FLOW

描述(改编自调查者摘要)：骨细胞占据液体 在矿化基质中填充陷窝，并由小管相互连接。 当骨被周期性加载时，液体在腔隙-管状网络中流动 从高基质应变区域到低基质应变区域，然后在 摇摆式时尚。尽管已经证明骨细胞会对 对于细胞内瞬时升高的稳定和脉动流体流动 钙浓度，旁分泌因子释放增加，并增加 基因转录，我们的初步数据表明这些反应可能是 与观察到的振荡流有根本的不同。到目前为止没有 已经设计了实验系统来研究对生理的反应 作为频率和流量的函数的振荡流体流动。为此， 首席调查员和他的合作调查员已经开发出一种 功能振荡流体流曝光装置。这使得他们能够 观察生理条件下细胞内钙离子的频率依赖性反应 振荡流体流动的级别。中心假设是生理上的 振荡流体流动的水平提供了一个重要的机制 机械转导，进而剪切应力水平、频率、时间 当然，低水平的稳定流动和细胞尺寸调节细胞 回应。为了验证这一假设，研究人员将使用以下组合 剪切力，改变水平和频率，并测量细胞信号和 新陈代谢。他们还感兴趣的是，细胞内钙离子 对振荡流动的响应之后是一个不应期，以及 振荡流体和低水平稳定流体在一起的可能性 协同效应。最后提出了研究细胞的影响的建议。 响应中的维度。我们的长期目标是了解机械 加载会影响骨骼的行为。

DESCRIPTION (adapted from the Investigator's abstract): Bone cells occupy fluid filled lacunae in the mineralized matrix and are interconnected by canaliculi. As bone is cyclically loaded, fluid flows in the lacunar-canalicular network from regions of high matrix strain to low matrix strain and back in an oscillatory fashion. Although it has been demonstrated that bone cells respond to steady and pulsatile fluid flow with a transient elevation in intracellular calcium concentration, increased release of paracrine factors, and increased gene transcription, our preliminary data indicate that these responses may be fundamentally different from those observed for oscillating flow. To date no experimental system has been designed to study responsiveness to physiologic oscillating fluid flow as a function of frequency and flow rate. To this end, the Principal Investigator and his co-investigators have developed a functioning oscillatory fluid flow exposure apparatus. This has allowed them to observe a frequency dependent intracellular calcium response to physiologic levels of oscillating fluid flow. The central hypothesis is that physiologic levels of oscillatory fluid flow provide an important mechanism of mechanotransduction, and furthermore shear stress level, frequency, time course, low level steady flow and cell dimensions modulate the cellular response. To test this hypothesis the investigators will apply combinations of shear stress, altering level and frequency, and measure cell signaling and metabolism. They are also interested in whether the intracellular calcium response to oscillating flow is followed by a refractory period as well as the possibility that oscillating and low level steady fluid are together synergistic. Finally studies are proposed to investigate the influence of cell dimension on response. The long-term goal is to understand how mechanical loading influences the behavior of bone.