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）：骨骼负荷减少会导致人类和大多数哺乳动物的肌肉萎缩和骨质流失。废用性肌肉萎缩和骨质疏松症对于长期制动和卧床休息的患者来说是严重的临床问题。熊和地松鼠在冬眠期间基本上不活动，但它们的骨量没有损失，肌肉萎缩也比在如此长时间的不活动期间预期的要少。这表明冬眠哺乳动物对肌肉骨骼废用具有独特的自然适应能力。尽管冬眠熊和地松鼠骨量的保存和肌肉萎缩的减轻已被记录，但这种重要适应的分子机制尚不清楚。我们的目标是通过转录变化识别生理相关的候选途径，并了解防止冬眠哺乳动物废用性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对冬季冬眠和夏季活跃的动物进行骨骼和肌肉转录变化的大规模筛选。全基因组转录谱将检测足够多的差异表达基因，进行全面的通路分析，阐明转录变化的功能意义。对具有不同冬眠模式的两个进化遥远物种之间的共同调控基因富集的功能基因组和通路进行比较，预计将揭示一般转录程序，具有未开发的潜力，可改善非冬眠哺乳动物废用性肌肉萎缩和骨质疏松症的治疗和预防，包括人类。。

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