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Regulation of Bone mass in Myostatin Deficient Mice

肌肉生长抑制素缺陷小鼠骨量的调节

基本信息

批准号：
6314913
负责人：
MARK W HAMRICK
金额：
$ 14.2万
依托单位：
KENT STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-04-11 至 2003-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6314913
关键词：
bone density bone development chordate locomotion densitometry disease /disorder model femur hormone regulation /control mechanism laboratory mouse muscle hypertrophy muscle strength radioimmunoassay somatotropin striated muscles transforming growth factors vertebrae

项目摘要

DESCRIPTION (Verbatim from the Applicant): The primary objective of the proposed Academic Research Enhancement Award is to investigate the influence of muscle strength on bone mass using a new mouse model. Specifically, this study evaluates multiple working hypotheses concerning the effects of increased muscle mass on activity level, bone cross-sectional geometry, bone mass, mineral content, and microstructure. These hypotheses are tested by comparing locomotor activity, growth hormone levels, and bone structure between mice deficient in growth and differentiation factor-8 (myostatin) and wild-type controls. Myostatin functions as a negative regulator of skeletal muscle growth and myostatin null mice show a doubling of muscle fiber size and number compared to normal mice. The primary factor leading to the onset of osteoporosis is bone loss. One preventative and therapeutic approach for minimizing the potentially disastrous affects of bone loss during life is to increase peak bone mass by increasing muscle strength. The proposed study, by critically evaluating the effects of increased muscle mass on bone strength during postnatal growth, will expand significantly upon our current understanding of the mechanisms important for generating and maintaining healthy bone structure in adults. This enhancement award will also engage undergraduate students from two programs at Kent State University, the McNair Scholars and Ohio Board of Regents STARS programs, in mentored bone biology research. The proposed project will therefore provide new training opportunities for students from populations traditionally underrepresented in the biomedical research community.

描述(来自申请者的逐字)：拟议的学术研究促进奖是为了调查使用一种新的小鼠模型研究肌肉力量对骨量的影响。具体地说，这项研究评估关于增加的影响的多个工作假设活动度水平的肌肉质量，骨的横截面几何形状，骨量，矿物质含量和显微结构。这些假设是通过比较来检验的小鼠之间的运动活动、生长激素水平和骨结构生长和分化因子-8(Myostatin)缺乏和野生型控制。肌肉生长抑制素对骨骼肌生长的负性调节作用而肌肉生长抑制素基因缺失的小鼠的肌肉纤维大小和数量增加了一倍与正常小鼠相比。导致疾病发生的主要因素骨质疏松症就是骨质流失。一种预防和治疗方法将生命中骨质流失的潜在灾难性影响降至最低是通过增加肌肉力量来增加峰值骨量。拟议的研究，由严格评估肌肉质量增加对骨强度的影响在出生后的生长过程中，将在我们目前的基础上显著扩大对生成和维护的重要机制的理解健康的成人骨骼结构。这项增强奖还将吸引来自肯特州立大学两个项目的本科生，麦克奈尔学者和俄亥俄州董事会明星计划，指导骨生物学研究。因此，拟议项目将提供新的培训。为来自传统上代表性不足的人群的学生提供机会生物医学研究界。