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: 10541830
• 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 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10541830
• 关键词: Acceleration; Advisory Committees; Affect; Age; Aging; Animal Model; Anti-Inflammatory Agents; 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 Diagnosis; Early treatment; Economic Burden; Elderly; Environment; Equilibrium; Exercise; Faculty; Future; Goals; Homeostasis; In Vitro; Incidence; Induction of Apoptosis; Inflammation; Inflammatory; Inflammatory Response; Injury; Interleukin-1; Massachusetts; Mechanics; Mentors; Metabolism; Modeling; Motion; Mus; Pain; Pathogenesis; Pathology; Pathway interactions; Phase; Phenotype; Play; Population; Posture; Predisposition; 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， 老化肌腱机械生物学领域。这项建议的目的是向我提供其余的 必要的研究培训，以便有效地过渡到独立。实现这一 目的，制定了培训方案，包括研究目标和实质性培训 活动拟议的科学研究将寻求开发一种新的体外肌腱损伤模型，重点是 年龄和压缩过载，以了解机械的后果，增加 压缩载荷环境对肌腱功能的影响，特别是与年龄相关的肩袖 退化该提案的中心假设是，慢性炎症环境和其他 与年龄相关的变化，肌腱细胞的过程，结合增加压缩负荷，由于穷人 姿势和肌肉组织，可能导致肩袖退化。我们的目标是调查这一假设， 使用小鼠肩袖建立了一个强大的压缩诱导肌腱损伤的体外模型， 使用该模型来解耦自然衰老和炎症在组织发育中的作用， 损害本申请中概述的项目将基础研究的重要性与 翻译为未来的诊断和治疗早期肌腱退变的治疗。 此外，本建议书还详细介绍了一系列职业发展活动，这些活动将帮助我沿着 成为独立调查员。马萨诸塞州理工学院为我提供了一个 特殊的环境，提供资源，调查拟议的科学研究和发展 成功职业发展所需的技能。此外，职业咨询团队，沿着 通过我专门在衰老生物学界发展的新的指导关系，将给我带来 经验和必要的建议，以加快我的职业生涯，并开始我自己的研究计划，作为一个 独立教师顾问。