EXTRACELLULAR CALCIUM AND OSTEOBLAST PROLIFERATION

描述(摘自应用程序)：此项目的目标是获得 对细胞外钙如何调节成骨细胞有扎实的了解 在分子水平上的扩散，通过在三个方面解决具体问题 关键领域：细胞表面钙感应、机制、细胞外 钙激活的有丝分裂信号通路与细胞外 钙激活基因转录。为了实现这一目标，我们建议1) 确定CAR在钙刺激的成骨细胞增殖中的作用。 我们将验证成骨细胞中是否存在CAR，如果是，确定是否 它在调节细胞有丝分裂的作用中具有重要作用。 细胞外钙；2)测定PKC异构体在细胞外钙通道中的作用 钙离子刺激成骨细胞增殖。我们将确定PKC是否 被细胞外钙激活，如果是这样的话，确定哪个PKC 异构体是否被激活以及它在功能上是否重要；3)定义 胞外基因转录调控的分子基础 钙。我们将在Fral中识别基础和钙反应元素 推动者。如果成功，我们将确定相互作用的转录因子 有了这些监管要素。我们还将确定哪个细胞内 信号通路介导细胞外钙对转录的影响 Fral基因的激活。这项研究的成功完成将有助于 建立细胞外钙刺激的分子机制 成骨细胞增殖，并将阐明钙在骨骼中的作用 改建。这项研究的结果也可能提供发展的机会 治疗骨质疏松症等骨病的治疗药物。

DESCRIPTION (Taken from the application): The goal of this project is to gain a solid understanding of how extracellular calcium regulates osteoblast cell proliferation at the molecular level by addressing specific questions in three key areas: cell surface calcium sensing, mechanism, extracellular calcium-activated mitogenic signal pathways, and extracellular calcium-activated gene transcription. To accomplish this, we propose to 1 ) determine the role of the CaR in calcium-stimulated osteoblast proliferation. We will verify the presence of the CaR in osteoblasts and if yes, determine if it is functionally important in mediating the mitogenic effects of extracellular calcium; 2) determine the role of PKC isoforms in calcium-stimulated osteoblast proliferation. We will determine if PKC is activated by extracellular calcium and if so, determine which of the PKC isoforms are activated and whether it is functionally important; 3) define the molecular basis of transcriptional regulation of the Fral gene by extracellular calcium. We will identify basal and calcium responsive elements in the Fral promoter. If successful, we will identify transcriptional factors interacting with these regulatory elements. We will also determine which intracellular signal pathways mediate the effects of extracellular calcium on transcriptional activation of the Fral gene. Successful completion of this study will help to establish the molecular mechanism of how extracellular calcium stimulates osteoblast proliferation and will shed light on the role of calcium in bone remodeling. The results of this study may also provide opportunities to develop therapeutic drugs for treatment of bone diseases such as osteoporosis.