OSMOLARITY AND CHONDROCYTE MECHANOTRANSDUCTION

描述（取自应用程序）： 背景：一个因素，这是一贯显示，影响软骨 生物合成是机械负荷，这是正常生物合成的结果。 联合动议然而，软骨细胞的物理环境是复杂的 在机械加载期间，不清楚哪些物理信号 软骨细胞有反应。在这项研究中，我们将重点放在渗透的潜力， 改变以充当相关的细胞信号。在机械加载期间， 软骨细胞的渗透环境被扰乱， 循环地从基质中取出，增加和减少局部蛋白聚糖 浓度，因此，离子强度和渗透压。渗透变化 在其他细胞类型中显示激活膜转运途径， 作为体积的一部分的细胞内信号传导因子水平增加 监管回应。然而，这些细胞的激活可能 信号事件也可能形成机械传导机制的一部分 由此机械负荷被转换成代谢反应。 假设：我们的中心假设是细胞外渗透压的变化， 如机械负荷诱导的，调节软骨细胞生物合成 通过参与音量调节的信号机制。目的：本研究 我们的目标是确定低渗透压对细胞内钙的影响， (Caa2+）、环磷酸腺苷（cAMP）和前列腺素E2 （PGE 2）水平（目标1），离子通道激活（目标2），并检查的作用， Ca ~（2+）、cAMP和PGE_2以及离子通道激活在两种容量调节中的作用（Aim 3)和软骨细胞生物合成（Aim 4）。这项研究的数据将为我们提供新的 深入了解软骨细胞如何应对渗透压挑战， 的渗透挑战，以修改软骨细胞的生物合成活性。 意义：这些研究的长期目标是增加我们的 了解机械负荷如何影响生物合成行为， 软骨细胞了解机械负荷等因素， 调节软骨周转，可能会提供深入了解 疾病如骨关节炎和类风湿性关节炎的病理生理学， 提供防止软骨破裂的治疗方法。

DESCRIPTION (Taken from the application): Background: One factor which is consistently shown to influence cartilage biosynthesis is mechanical loading, which occurs as a consequence of normal joint motion. However, the physical environment of the chondrocyte is complex during mechanical loading and it is unclear to which physical signals chondrocytes respond. In this study we will focus on the potential for osmotic change to act as a relevant cellular signal. During mechanical loading the osmotic environment of the chondrocyte is perturbed as fluid is forced into and out of the matrix cyclically, increasing and decreasing local Proteoglycans concentrations and therefore, the ionic strength and osmolarity. Osmotic change has been shown in other cell types to activate membrane transport pathways and increase levels of intracellular signaling factors as part of a volume regulatory response. It is possible, however, that activation of these signaling events might also form part of a mechanotransduction mechanism whereby mechanical loads are transduced into a metabolic response. Hypothesis: Our central hypothesis is that changes in extracellular osmolarity, as would be induced by mechanical loading, regulate chondrocyte biosynthesis through signaling mechanisms involved in volume regulation. Aims: In this study our goal is to determine the effect of hypo-osmolarity on intracellular calcium (Caa2+), adenosine 3', 5'-cyclic monophosphate (cAMP) and prostaglandin E2 (PGE2) levels (Aim 1), ion channel activation (Aim 2), and examine the role of Ca2+, cAMP and PGE2 and ion channel activation in both volume regulation (Aim 3) and chondrocyte biosynthesis (Aim 4). Data from this study will give us new insight into how chondrocytes contend with osmotic challenge, and the ability of osmotic challenge to modify the biosynthetic activity of chondrocytes. Significance: The long term goal of these studies is to increase our understanding of how mechanical loading influences the biosynthetic behavior of chondrocytes. An understanding of factors, such as mechanical load, which regulate cartilage turnover, could potentially provide insights into the pathophysiology of diseases such as osteoarthritis and rheumatoid arthritis and provide treatments which prevent cartilage breakdown.