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

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，能够为 老化肌腱机械生物学领域。这项提议的目的是为我提供剩余的 进行必要的研究培训，以便有效地向独立过渡。要做到这一点 目标，制定了由研究目标和实质性训练组成的训练方案 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 年龄和压缩超载，以机械地理解增加的后果 压缩负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 与年龄相关的腱细胞突起的变化，结合由于不良的压缩负荷增加 姿势和肌肉结构，可能会导致肩袖退化。我们的目标是通过以下方式研究这一假设 使用小鼠的肩袖建立了一个强大的体外受压肌腱损伤模型，并 使用这个模型来分离自然衰老和炎症在组织发育中的作用 损坏。本申请中概述的项目将基础基础研究的重要性与 对今后早期肌腱退行性变的诊断和治疗有一定的指导意义。 此外，这份提案详细介绍了一系列职业发展活动，这些活动将帮助我在通往 成为一名独立的调查员。麻省理工学院为我提供了 特殊环境，提供资源以调查拟议的科学研究并制定 成功的职业发展所必需的技能。此外，集结的职业顾问团队，以及 随着我在老龄化生物界特别发展的新的指导关系，将给我 经验和建议是加速我的职业生涯和开始我自己的研究计划所必需的 独立教师顾问。

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.