Roles of PTH/PTHrP Receptors in Osteoblastic Cells

性状（由申请人提供）：甲状旁腺激素（PTH）具有 对骨骼的作用复杂且仅部分了解，主要针对 成骨细胞谱系。PTH对骨的许多作用是由 PTH/PTHrP受体（PPR）。这项研究旨在探讨监管 成骨细胞的承诺，增殖，分化和死亡的PPR， 以及细胞对破骨细胞生成和造血的调节， 成骨细胞谱系的不同成熟阶段。为了研究 这些问题，细胞从转基因小鼠，其中一个组成性活性 在成骨细胞谱系中表达的PPR形式将被分离， 表征了这些突变小鼠具有惊人的表型， 骨、成骨细胞、基质细胞和破骨细胞增加。这个项目 将使用一个体外系统来了解这些细胞在体内的作用。 vivo.通过研究这些细胞的行为，该项目旨在定义 细胞和分子机制，介导的PPR的作用， 成骨细胞此外，对PTH影响的更好理解可能 为常见代谢性疾病的治疗进展提供基础 骨疾病，如骨质疏松症。 候选人表示，研究项目和教学活动 建议将帮助她获得必要的专业知识，以追求职业生涯 专注于临床相关性的实验室研究。通过分析 所获得的数据、与导师的讨论和正式的教学培训， 她将能够扩展她在分子遗传学和发育方面的知识， 并在细胞生物学、细胞间相互作用和 发信号。来自KO 8奖的支持将有助于完成本提案，并帮助申请人独立地作为PTH作用和骨与矿物质代谢领域的研究者，临床医生和教师。

DESCRIPTION (provided by the applicant): Parathyroid hormone (PTH) has a complex and only partially understood action on bone, which mainly targets the osteoblast lineage. Many of the actions of PTH on bone are mediated by the PTH/PTHrP receptor (PPR). The proposed study aims to investigate the regulation of osteoblasts commitment, proliferation, differentiation and death by the PPR, as well as regulation of osteoclastogenesis and hematopoiesis by cells at different stages of maturation in the osteoblast lineage. In order to study these questions, cells from transgenic mice in which a constitutively active form of the PPR is expressed in the osteoblast lineage will be isolated and characterized. These mutant mice have a striking phenotype, with enormous increases in bone, osteoblasts, stromal cells and osteoclasts. This project will use an in vitro system to understand what these cells are shown to do in vivo. By studying the behavior of these cells, this project aims to define the cellular and molecular mechanisms that mediate the role of the PPR in osteoblasts. In addition, an improved understanding of the effects of PTH may provide the basis for advances in the treatment of common forms of metabolic bone disease, such as osteoporosis. The candidate states that the research project and the didactic activities proposed will help her acquire the expertise necessary to pursue a career focused on laboratory-based research of clinical relevance. Through analysis of the data obtained, discussion with her mentors and formal didactic training, she will be able to expand her knowledge of molecular genetics and development and become experienced in the field of cell biology, cell-cell interaction and signaling. Support from a KO8 award will assist in the completion of thi s proposal, and help the applicant to set out independently as an investigator, clinician and teacher in the field of PTH action and bone and mineral metabolism.