P01-Pathogenesis and Prevention of Osteoporosis

整体程序描述(摘自应用程序)：此程序 项目应用代表着一个协调、协作和 多学科方法，利用公共资源、设施和 支持与发病机制相关的科学研究人员的仪器 骨质疏松症。该应用程序由四个高度集成的应用程序组成 科学项目和三个支持核心设施(行政、 分子组织学和转基因动物和分子核心)。中环 计划项目的主题是骨质疏松症的发病机制 既与促进骨吸收的分解代谢因子的相互作用有关，也与促进骨吸收的分解代谢因子相互作用有关 导致合成代谢活动的丧失。这些因素，既包括系统激素，也包括 局部细胞因子调节破骨细胞和成骨细胞的分化 血统细胞和这些细胞的生物学功能。一种对 这些因素及其在骨重建中的作用将有助于阐明 骨质疏松的发病机制。此外，对阻断分子的干预 致病因素或增强合成代谢活性会有治疗作用 这意味着什么。这可以通过体细胞基因治疗来实现，一旦 开发这种策略所需的细胞和分子步骤被开发出来。 本申请的科学项目是：(1)糖皮质激素和 成骨细胞凋亡，(2)雌激素对细胞因子反应性的调节 骨：破骨细胞的形成，(3)胰岛素样生长因子和 糖皮质激素对骨重建的影响，以及(4)骨祖细胞的植入 骨骼中的细胞。我们相信我们的调查人员、研究人员之间的互动 面向中心主题的生产力和新的合作将是 计划项目机制极大地促进了这一进程。

DESCRIPTION OF THE OVERALL PROGRAM (taken from the application): This program project application represents a coordinated, collaborative and multidisciplinary approach that utilizes common resources, facilities and instrumentation to support scientific investigators related to the pathogenesis of osteoporosis. This application is comprised of four highly integrated scientific projects and three supporting core facilities (Administration, Molecular Histology and Transgenic Animal and Molecular Cores). The central theme of the ?program project is that the pathogenesis of osteoporosis is due both to the interaction of catabolic factors that increase bone resorption and to the loss of anabolic activities. These factors, both systemic hormones and local cytokines, modulate the differentiation of osteoclast and osteoblast lineage cells and the biological function of these cells. An understanding of these factors and their actions on bone remodeling will help elucidate the pathogenesis of osteoporosis. Moreover, intervention with molecules that block pathogenic factors or enhance anabolic activities will have therapeutic implications. This could be accomplished by somatic gene therapy once the cellular and molecular steps required to develop such a strategy are developed. The scientific projects of this application are: (1) Glucocorticoids and osteoblast apoptosis, (2) Estrogen regulation of cytokine responsiveness in bone: osteoclastogenesis, (3) The roles of insulin-like growth factor and glucocorticoids on bone remodeling, and (4) Engraftment of osteoprogenitor cells in bone. We believe that interactions among our investigators, research productivity towards the central theme and new collaborations will be facilitated greatly by the program project mechanism.