MECHANOTRANSDUCTION IN BONE VIA OSCILLATING FLUID FLOW

通过振荡流体流进行骨骼中的机械传导

• 批准号: 6128699
• 负责人: Christopher Rae Jacobs
• 金额: $ 4.45万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-15 至 2001-01-12
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6128699
• 关键词: biological signal transduction; biomechanics; biophysics; bone metabolism; calcium flux; cell membrane; cell morphology; confocal scanning microscopy; digital imaging; electrophysiology; enzyme linked immunosorbent assay; fluid flow; human tissue; messenger RNA; oscillatory blood flow; osteoblasts; osteocytes; osteopontin; physiologic stressor; polymerase chain reaction; prostaglandin E; tissue /cell culture

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.

描述（改编自研究者摘要）：骨细胞占据液体 填充矿化基质中的腔隙，并通过小管相互连接。 当骨受到周期性载荷时，液体在腔隙-小管网络中流动 从高基质应变区域到低基质应变区域， 振荡方式尽管已经证明骨细胞对 到稳定和脉动的流体流动，细胞内 钙浓度，旁分泌因子释放增加， 基因转录，我们的初步数据表明，这些反应可能 与振荡流观察到的情况有根本不同。迄今没有 设计了一个实验系统，用于研究对生理 作为频率和流速的函数的振荡流体流。为此目的， 首席研究员和他的合作研究员已经制定了一个 功能振荡流体流暴露装置。这使他们能够 观察到频率依赖性细胞内钙对生理 振荡流体流的水平。核心假设是， 振荡流体流的水平提供了 机械转导，以及剪切应力水平、频率、时间 当然，低水平的稳定流动和细胞尺寸调节了细胞的 反应为了验证这一假设，研究人员将应用以下组合： 剪切应力，改变水平和频率，并测量细胞信号传导， 新陈代谢.他们还对细胞内钙离子是否 对振荡流的响应之后是不应期， 振荡流体与低液位稳定流体共存的可能性 协同作用。最后提出了研究细胞的影响， 尺寸响应。长期目标是了解机械 载荷影响骨的行为。