Overcoming Disuse Atrophy and Osteoporosis in Hibernating Mammals

克服冬眠哺乳动物的废用性萎缩和骨质疏松症

基本信息

批准号：
8828570
负责人：
Vadim Fedorov
金额：
$ 16.5万
依托单位：
UNIVERSITY OF ALASKA FAIRBANKS
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8828570
关键词：
Animals Base Pairing Bed rest Bioinformatics Biological Preservation Black Bear Clinical Data Development Distant Disuse Atrophy Drug Compounding Foundations Future Gene Expression Gene Expression Profile Genes Genetic Transcription Genomics Goals Health Hibernation Human Immobilization Length Mammals Maps Mechanics Metabolic Pathway Modeling Molecular Molecular Profiling Muscle Muscular Atrophy Musculoskeletal Osteoporosis Pathway Analysis Pathway interactions Patients Prevention Process Reading Regulator Genes Research Resources Sampling Signal Pathway Skeletal Muscle Skeletal bone Skeleton Spermophilus Technology Testing Tissue-Specific Gene Expression Translating Ursidae Family arctic ground squirrel attenuation base bone bone disuse atrophy bone loss bone mass cost effective differential expression follow-up genome sequencing genome-wide genome-wide analysis improved insight knowledge base muscle form muscle strength next generation sequencing novel overexpression prevent programs research study skeletal therapeutic target tool transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): Reduced skeletal loading leads to muscle atrophy and bone loss in humans and most mammals. Disuse muscle atrophy and osteoporosis represent significant clinical problem for patients during prolonged periods of immobilization and bed rest. Bears and ground squirrels are largely inactive during hibernation, but they show no loss in bone mass and less muscle atrophy than would be anticipated over such a prolonged period of physical inactivity. This suggests that hibernating mammals have unique natural adaptation to musculoskeletal disuse. Although preservation of bone mass and attenuation of muscle atrophy in hibernating bears and ground squirrels have been documented, molecular mechanisms underlying this important adaptation are not known. Our goal is to identify through transcriptional changes physiologically relevant candidate pathways and understand molecular mechanisms preventing disuse muscle atrophy and bone loss in hibernating mammals. Advantage of the next generation sequencing tools will be used to conduct large scale screens of transcriptional changes in bone and muscle comparing winter hibernating and summer active animals. Genome-wide transcriptional profiling will detect sufficiently large number of differentially expressed genes for comprehensive pathway analysis elucidating functional significance of transcriptional changes. Comparison of functional gene groups and pathways enriched by co regulated genes between two evolutionary distant species with different hibernation modes is expected to reveal general transcriptional program with untapped potential for development of improved treatment and prevention of disuse muscle atrophy and osteoporosis in non-hibernating mammals, including humans. .

描述（由申请人提供）：减少骨骼负荷会导致人类和大多数哺乳动物的肌肉萎缩和骨质流失。在长期固定和床休息期间，肌肉萎缩和骨质疏松症代表了患者的重大临床问题。在冬眠期间，熊和地松鼠在很大程度上是不活跃的，但是它们在骨骼质量中没有损失，肌肉萎缩少于在如此长时间的身体不活跃期间所预期的。这表明冬眠的哺乳动物具有独特的自然适应肌肉骨骼废物。尽管已经记录了骨量和肌肉萎缩的衰减，但已记录在冬眠的熊和地松鼠中，但尚不清楚这种重要适应性的分子机制。我们的目标是通过转录变化生理相关的候选途径来识别，并了解冬眠哺乳动物中肌肉萎缩和骨质流失的分子机制。下一代测序工具的优势将用于进行骨和肌肉转录变化的大规模筛选，以比较冬季冬眠和夏季活性动物。全基因组的转录分析将检测到足够多的差异表达基因，以阐明转录变化的功能意义。预期具有不同冬眠模式的两个进化远处的物种之间富含CO调节基因的功能基因组和途径的比较，预计将揭示一般的转录程序，并且在包括人类在内的非疗程的哺乳动物（包括人类）的非养生哺乳动物中未开发的潜力，可提高改善治疗和预防残疾肌肉萎缩和骨质疏松症。。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Comparative functional genomics of adaptation to muscular disuse in hibernating mammals.

DOI：
10.1111/mec.12963
发表时间：
2014-11
期刊：
Molecular ecology
影响因子：
4.9
作者：
Fedorov VB;Goropashnaya AV;Stewart NC;Tøien Ø;Chang C;Wang H;Yan J;Showe LC;Showe MK;Barnes BM
通讯作者：
Barnes BM