Osteocyte Regulation of Bone/Muscle with Age

骨细胞随年龄对骨/肌肉的调节

基本信息

批准号：
8917675
负责人：
Lynda F Bonewald
金额：
$ 6.04万
依托单位：
UNIVERSITY OF MISSOURI KANSAS CITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8917675
关键词：
Acids Address Adipose tissue Age Age Factors Aging Alleles American Animals Anti-Inflammatory Agents Anti-inflammatory Apoptosis Binding Biology Blood Blood Circulation Bone Surface Bone Tissue Brain Caring Cell Death Cell physiology Cells Cessation of life Clinical Communication Conditioned Culture Media Coupling Data Development Disease Distant Dyes Education Elderly Endocrine Endocrine Glands Environment Exercise Failure Fatty acid glycerol esters Fibroblasts Foundations Fracture Gastrointestinal tract structure Genes Gland Grant Harvest Health Hip Fractures Histology Homeostasis Incidence Individual Injection of therapeutic agent Injury International Investigation Kidney Knowledge Lead Leadership Life Link Liver Manuscripts Mechanics Mediator of activation protein Molecular Molecular Weight Morbidity - disease rate Mus Muscle Muscle Cells Muscle Fibers Muscle Weakness Muscle function Muscular Atrophy Musculoskeletal Diseases Musculoskeletal System Organ Osteoblasts Osteocalcin Osteocytes Osteogenesis Osteoporosis Pathway interactions Patients Phenotype Plant Resins Play Population Postdoctoral Fellow Predisposition Preparation Prevention Principal Investigator Production Program Research Project Grants Proteins Quality of life Reactive Oxygen Species Regulation Reporting Research Personnel Risk Role Schedule Series Signal Transduction Site Skeletal Muscle Skeletal bone Skeleton Stream Students Syndrome System Therapeutic Tissues Transgenic Organisms Travel Vascular System Veins Writing age effect aged aging population base beta catenin blood glucose regulation bone bone cell bone loss bone mass brain tissue clinical practice combat cytokine design diet and exercise experience falls improved inhibitor/antagonist innovation juvenile animal meetings mortality muscle form novel therapeutic intervention novel therapeutics operation paracrine particle premature progenitor programs release factor research study response sarcopenia skeletal skills success tool

项目摘要

DESCRIPTION (provided by applicant): Osteoporosis and sarcopenia are major clinical problems in the aging population and in many patients these two conditions occur concurrently. This combination results in instability, susceptibility to falls and consequently to fracture, morbidity, and premature death. It is unclear whether one condition precedes the other or if the conditions are linked. The traditional view of skeletal muscle and bone interaction is that skeleta muscle loads bone and bone provides an attachment site for muscle. The mechanical perspective implies that as muscle function declines, this would result in decreased loading of the skeleton and therefore would result in a decrease in bone mass. However, muscle atrophy alone cannot fully explain the totality of osteoporosis and, reciprocally, aging associated decreases in bone mass do not fully explain sarcopenia. Our preliminary data suggest that soluble factors may play a role in crosstalk between bone and muscle. The hypothesis for the Program Project is that there is an endocrine loop between muscle and bone through the production of systemic factors by each tissue that are critical regulatory factors for function in the other tissue. The osteocyte response to mechanical loading by the action of muscles is modified by these muscle secreted factors. In turn, the osteocyte regulates both osteoblast and muscle cell function through modulators of the Wnt/beta-catenin pathway. A series of experiments to examine the role of the osteocyte in muscle-bone crosstalk and what happens with aging are proposed. The specific aims are 1). Determine the effects of muscle on osteoblast/osteocyte function with aging, 2). Determine the effects of osteocytes on muscle mass and function with aging, 3). Examine osteocyte regulation of osteoblast function with aging and how this is regulated or influenced by muscle-bone crosstalk, and 4). Determine the effects of mechanical loading on osteocyte regulation of muscle mass and function with aging. This program project is innovative in concept, preliminary data, approach, tools, interdisciplinarity, and cadre of investigators. The results of these experiments should lead to novel therapeutics for the prevention and treatment of both osteoporosis and sarcopenia.

描述（由申请人提供）：骨质疏松症和肌肉减少症是老龄化人群中的主要临床问题，并且在许多患者中这两种情况同时发生。这种组合导致不稳定、容易跌倒，从而导致骨折、发病和过早死亡。目前尚不清楚一个条件是否先于另一个条件，或者这些条件是否相互关联。骨骼肌和骨骼相互作用的传统观点是骨骼肌负载骨骼，骨骼为肌肉提供附着位点。力学角度意味着，随着肌肉功能下降，这将导致骨骼负荷减少，从而导致骨量减少。然而，单独的肌肉萎缩并不能完全解释骨质疏松症的全部情况，相反，衰老相关的骨量减少也不能完全解释肌少症。我们的初步数据表明可溶性因子可能在骨骼和肌肉之间的串扰中发挥作用。该计划项目的假设是，通过每个组织产生的系统因子，肌肉和骨骼之间存在内分泌循环，这些系统因子是其他组织功能的关键调节因子。骨细胞对肌肉动作产生的机械负荷的反应被这些肌肉分泌因子改变。反过来，骨细胞通过 Wnt/β-连环蛋白途径的调节剂调节成骨细胞和肌肉细胞的功能。提出了一系列实验来检查骨细胞在肌肉-骨骼串扰中的作用以及衰老过程中会发生什么。具体目标是1）。确定肌肉对成骨细胞/骨细胞功能随衰老的影响，2)。确定骨细胞对肌肉质量和衰老功能的影响，3)。检查随着衰老，骨细胞对成骨细胞功能的调节，以及肌骨串扰如何调节或影响这一过程，4)。确定机械负荷对骨细胞对肌肉质量和功能随衰老的调节的影响。该项目在概念、初步数据、方法、工具、跨学科性和研究人员队伍方面都有创新。这些实验的结果应该会产生预防和治疗骨质疏松症和肌肉减少症的新疗法。