EXTRACELLULAR CALCIUM AND OSTEOBLAST PROLIFERATION

描述（取自应用程序）：该项目的目标是获得 深入了解细胞外钙如何调节成骨细胞 通过解决三个方面的具体问题， 关键领域：细胞表面钙传感，机制，细胞外 钙激活的促有丝分裂信号通路，和细胞外 钙激活基因转录。为此，我们建议：（1） 确定钙受体在钙刺激成骨细胞增殖中的作用。 我们将验证成骨细胞中CaR的存在，如果是， 它在介导有丝分裂效应方面具有重要功能 细胞外钙; 2）确定PKC亚型的作用， 钙刺激的成骨细胞增殖。我们将确定PKC是否 激活细胞外钙，如果是这样，确定哪些PKC 同种型被激活，以及它是否在功能上重要; 3）定义 细胞外因子对Fral基因转录调控的分子基础 钙我们将确定基础和钙反应元件在FRAL 启动子如果成功，我们将确定转录因子相互作用 有了这些规则元素。我们还将确定哪些细胞内 信号通路介导细胞外钙离子对转录的影响 激活Fral基因。成功完成这项研究将有助于 建立细胞外钙离子如何刺激 成骨细胞增殖，并将阐明钙在骨中的作用 重塑这项研究的结果也可能提供发展的机会 用于治疗骨质疏松症等骨疾病的治疗药物。

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.