Development of In Vitro Compression-Induced Rotator Cuff Injury Model: Aging and Inflammation in Tendon Degeneration

体外压缩引起的肩袖损伤模型的开发：肌腱退变中的衰老和炎症

• 批准号: 10304363
• 负责人: Brianne Kathryn Connizzo
• 金额: $ 24.9万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10304363
• 关键词: Advisory Committees; Affect; Age; Aging; Animal Model; Anti-Inflammatory Agents; Apoptosis; Apoptotic; Basic Science; Biological Models; Biology; Biology of Aging; Cartilage; Cell Death; Cell Density; Cells; Chronic; Clinic; Clinical; Clinical Research; Communities; Development; Dexamethasone; Diagnosis; Disease; Disease Progression; Dose; Early treatment; Economic Burden; Elderly; Environment; Equilibrium; Exercise; Faculty; Future; Goals; Homeostasis; In Vitro; Incidence; Inflammation; Inflammatory; Inflammatory Response; Injury; Institutes; Interleukin-1; Lead; Massachusetts; Mechanics; Mentors; Metabolism; Modeling; Motion; Mus; Pain; Pathogenesis; Pathology; Pathway interactions; Phase; Phenotype; Play; Population; Posture; Process; Property; Proteoglycan; Protocols documentation; Regimen; Rehabilitation therapy; Reporting; Research; Research Personnel; Research Training; Resources; Role; Rotator Cuff; Series; Shoulder Pain; Stress; TNF gene; Technology; Tendon Injuries; Tendon structure; Therapeutic; Time; Tissues; Training; Training Activity; Translations; Work; age effect; age related; aged; aging population; anti aging; career; career development; deprivation; disability; experience; fluid flow; in vitro Model; in vivo; inflammatory milieu; mechanical load; musculoskeletal injury; nanomechanics; novel; prevent; programs; repaired; response; rotator cuff injury; skills; therapeutic target; tissue degeneration

Project Summary My ultimate career goal is to become a successful independent investigator who can contribute significantly to the field of aging tendon mechanobiology. The objective of this proposal is to provide me with the remaining necessary research training in order to make the transition to independence effectively. To achieve this objective, a training regimen has been developed, consisting of research aims and substantial training activities. The proposed scientific studies will seek to develop a novel in vitro tendon injury model focused on age and compressive overload, in order to understand mechanistically the consequences of an increased compressive loading environment on tendon function, specifically as it relates to age-related rotator cuff degeneration. The central hypothesis of the proposal is that the chronic inflammatory environment and other age-related changes in tenocyte processes, combined with an increase in compressive loading due to poor posture and musculature, may lead to rotator cuff degeneration. We aim to investigate this hypothesis by creating a powerful in vitro model of compression-induced tendon damage using the murine rotator cuff, and to use this model to decouple the contributions of natural aging and inflammation in the development of tissue damage. The project outlined in this application combines fundamental basic research importance with translation directed toward the future diagnosis and therapeutic treatment of early stage tendon degeneration. In addition, this proposal details a series of career development activities that will aid me along the journey to becoming an independent investigator. The Massachusetts Institute of Technology provides me with an exceptional environment, providing the resources to investigate the proposed scientific studies and develop the skills necessary for successful career development. Furthermore, the assembled career advisory team, along with new mentoring relationships I am developing specifically in the aging biology community, will give me the experience and advising necessary to accelerate my career and begin my own research program as an independent faculty advisor.

项目摘要 我的最终职业目标是成为一名成功的独立调查员，他可以为 衰老肌腱机械生物学领域。该提议的目的是为我提供其余的 必要的研究培训，以便有效地过渡到独立性。实现这一目标 目标是一种培训方案，包括研究目的和实质性培训 活动。拟议的科学研究将寻求开发一个针对的新型体外肌腱损伤模型 年龄和压缩超负荷，以便从机械上理解增加的后果 肌腱功能上的压缩加载环境，特别是与年龄相关的肩袖有关 退化。该提案的核心假设是慢性炎症环境和其他 与年龄相关的Tenocyte工艺的变化，加上由于较差的压缩负荷增加 姿势和肌肉组织可能导致肩袖变性。我们旨在通过 创建强大的体外模型，用于使用鼠肩袖袖口，并 使用此模型将自然衰老和炎症在组织发展中的贡献解脱 损害。该应用程序中概述的项目结合了基本的基础研究重要性和 翻译针对未来的诊断和早期肌腱变性的治疗治疗。 此外，该建议详细介绍了一系列职业发展活动，这将有助于我在旅途中 成为独立研究者。马萨诸塞州理工学院为我提供了 特殊的环境，提供资源来调查拟议的科学研究并发展 成功发展职业发展所需的技能。此外，集会的职业咨询团队 随着我在衰老生物学社区中专门发展的新的指导关系，将为我提供 经验和建议必须加快我的职业并开始自己的研究计划 独立教师顾问。