Serotonin as a Regulator of Bone Mass Accrual: Basic and Clinical

血清素作为骨量增长的调节剂：基础和临床

基本信息

批准号：
8302302
负责人：
Gerard Karsenty
金额：
$ 135.42万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8302302
关键词：
Address Advisory Committees Aging Animals Biology Bone Tissue Bone remodeling Brain Brain Stem Cell Proliferation Regulation Clinical Data Development Disease Equipment Estrogens Evaluation Event Failure Goals Hormones Human Hydroxylation Hypothalamic structure Laboratories Leptin Link Maintenance Medical Mental Depression Mission Molecular Molecular Genetics Mutant Strains Mice Neurons Osteoblasts Osteogenesis Osteoporosis Output Pathogenesis Peripheral Play Positioning Attribute Preparation Principal Investigator Procedures Proteins Quality Control Regulation Research Role Schedule Seminal Serotonin Serotonin Production Services Signal Transduction Site Specimen Staining method Stains System Testing Therapeutic Time Tryptophan Work base bone bone cell bone mass bone quality contextual factors cost gain of function genetic analysis improved indexing insight leptin receptor long bone loss of function mutation meetings morphometry novel programs research study ventromedial hypothalamic nucleus

项目摘要

The overall goal of this Program Project Application is to improve our understanding of the genetic and molecular control of bone remodeling in the context of aging by identifying a novel regulator, elucidating its modes of action and documenting its clinical importance. The four projects will examine (1) the role of brain-derived serotonin in the regulation of bone formation and its mechanisms of action (Karsenty); (2) the molecular mechanisms whereby gut-derived serotonin regulates osteoblast proliferation and bone formation (Kousteni); (3) the functional hierarchy between brain-derived and gut-derived serotonin as well as the therapeutic potential of inhibiting the synthesis of gut-derived serotonin; (4) the involvement of serotonin in depression-induced and gonadal-failure-induced osteoporosis in humans (Bilezikian). These projects will be supported by two essential cores. Core A is an administrative core integrating a biostatistical support, core B is a Bone Morphometry Core providing histomorphometry and microCT analyses. The coordination of the projects will be performed by the program director. This will be facilitated by the synergy and complementary between the projects, by our monthly meetings, by our interaction with the internal (monthly) and external (yearly) scientific advisory boards and by the supporting roles played by the cores. Together our studies should provide important and novel insights in the genetic and molecular control of bone remodeling as well as in the pathogenesis and treatment of osteoporosis, a major disease of aging.

该计划项目申请的总体目标是通过识别新型调节剂、阐明其作用模式并记录其临床重要性，提高我们对衰老背景下骨重塑的遗传和分子控制的理解。这四个项目将研究（1）脑源性血清素在骨形成调节中的作用及其作用机制（Karsenty）；（2）肠源性血清素调节成骨细胞增殖和骨形成的分子机制（Kousteni）；（3）脑源性和肠源性血清素之间的功能层次以及抑制肠源性血清素合成的治疗潜力； (4) 血清素参与抑郁诱发和性腺衰竭诱发的人类骨质疏松症（Bilezikian）。这些项目将得到两个重要核心的支持。核心 A 是集成生物统计支持的管理核心，核心 B 是提供组织形态测定和 microCT 分析的骨形态测定核心。项目的协调将由项目总监进行。项目之间的协同作用和互补性、我们的每月会议、我们与内部（每月）和外部（每年）科学顾问委员会的互动以及核心发挥的支持作用将促进这一点。我们的研究应该共同为骨重塑的遗传和分子控制以及骨质疏松症（一种主要的衰老疾病）的发病机制和治疗提供重要而新颖的见解。