权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

HMGB1 Mediates the Onset of Loading-Induced Tendon Injury

HMGB1 介导负荷引起的肌腱损伤的发生

基本信息

批准号：
9318431
负责人：
JAMES H-C. WANG
金额：
$ 17.08万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-20 至 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9318431
关键词：
Adverse effects Affect American Athletic Binding Proteins Biological Assay Biological Models Biological Process Cell Proliferation Cells Cellular Stress Chronic Clinic Clinical Collagen Fiber DNA-Binding Proteins Development Dinoprostone Enzyme-Linked Immunosorbent Assay Enzymes Event Exposure to Fibroblasts Frequencies Gene Expression General Population Glycyrrhizic Acid HMGB1 Protein Healthcare Hemorrhage Immune Impairment Infiltration Inflammation Inflammation Mediators Inflammatory Injury Interstitial Collagenase Kidney Kidney Failure Lead Leukocytes Liver Lung Mammalian Cell Measures Mechanical Stress Mechanics Mediating Modeling Molecular Molecular Analysis Mus Muscle Nuclear Nucleosomes Occupational Organ PECAM1 gene PTGS2 gene Patients Pattern Periodontal Ligament Pharmacotherapy Prevention strategy Production Protocols documentation Recruitment Activity Reporting Research Role Running Signal Transduction Signaling Molecule Site Sports Staining method Stains Sterility Stress Stromelysin 1 Structure Tendinopathy Tendon Injuries Tendon structure Testing Tissue Inhibitor of Metalloproteinase-1 Tissues Translations Trauma Ulcer Western Blotting angiogenesis bone cell injury collagenase 3 cost extracellular in vitro Model in vivo inhibitor/antagonist injured innovation macrophage mechanical force mechanical load novel palliative prevent response treadmill treatment strategy young adult

项目摘要

Tendon injuries affect millions of Americans in both occupational and athletic settings and cost billions of healthcare dollars every year. While mechanical loading is considered as a major causative factor responsible for tendon injuries, the molecular mechanisms that initiate translation of mechanical loading into tendon injuries remain unknown. In this study, we offer an innovative hypothesis that HMGB1, a well-established inflammation-related nuclear binding protein in major tissues and organs, is responsible for the onset of the tendon inflammatory cascade due to excessive mechanical loading placed on tendons. Specifically, we propose two aims in this study: 1) to determine the effects of various mechanical loading conditions on tendon cells using a novel in vitro model system; and 2) to determine the effects of mechanical over-loading conditions on mouse tendons in vivo using a well-established mouse treadmill running model. Cellular and molecular analyses will be performed to define the HMGB1 signaling cascade. This study represents the first efforts to determine the role of HMGB1 in the onset of tendon injuries. The successful completion of this study will reveal the early signaling mechanism that is responsible for the development of full blown tendinopathy often seen down-the-road in tendinopathic patients. This research endeavor will lead to new prevention and treatment strategies such as targeting HMGB1 by blocking its action that will be more effective than current tendinopathy treatment options, which are largely palliative.

肌腱损伤影响了数百万美国人在职业和运动设置和成本数十亿美元，每年的医疗费用。而机械载荷被认为是一个主要的致病因素负责对于肌腱损伤，启动机械负荷转化为肌腱损伤的分子机制仍然未知。在这项研究中，我们提出了一个创新的假设，即HMGB 1，一个公认的炎症相关的核结合蛋白在主要组织和器官，是负责的发病，由于施加在肌腱上的过度机械负荷导致的肌腱炎症级联反应。我们特别本研究提出两个目的：1）确定各种机械载荷条件对预应力筋的影响细胞使用一种新的体外模型系统;和2）以确定机械过载条件的影响在小鼠肌腱在体内使用一个完善的小鼠跑步机运行模型。细胞和分子将进行分析以确定HMGB 1信号级联。这项研究代表了确定HMGB 1在肌腱损伤发病中的作用的第一次努力。的这项研究的成功完成将揭示早期信号机制，负责肌腱病患者中经常出现的全面肌腱病的发展。本研究奋进将导致新的预防和治疗策略，例如通过阻断HMGB 1的作用来靶向它这将比目前的肌腱病治疗方案更有效，目前的治疗方案主要是姑息性的。