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: 10757182
• 负责人: Brianne Kathryn Connizzo
• 金额: $ 8.25万
• 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/10757182
• 关键词: Acute; Affect; Age; Aging; Basic Science; Biological; Biological Models; Biology; Bioreactors; Chronic; Clinical Research; Development; Diagnosis; Disease; Early treatment; Environment; Extracellular Matrix; Future; Goals; In Vitro; Incubators; Inflammation; Injury; Mechanics; Modeling; Pain; Pathogenesis; Pathway interactions; Population; Posture; Process; Protocols documentation; Rehabilitation therapy; Role; Rotator Cuff; Sampling; Tendon structure; Therapeutic; Tissues; Translations; Work; age related; aging population; anti aging; disability; inflammatory milieu; mechanical load; prevent; response; rotator cuff injury

PROJECT SUMMARY The long-term goal of this project is to understand age-related biological changes negatively impact tendon mechanosensation and extracellular matrix remodeling. This application lays out a strategy 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 tendon degeneration. We will first harness our in vitro culture models along with incubator-housed controllable loading bioreactors to create compression-induced tendon damage in tendon explants. Specifically, we are building the first-of-its-kind dual axis mechanical loading bioreactor for tendon explant tissue to apply simultaneous tensile and compressive loading to samples. Using this bioreactor, we will establish models of compression- induced damage by varying loading duration (acute versus chronic) and maximum strain level (low and high). We will then use these models 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. If successful, this work will fully decouple the effects of inflammation and mechanical overload on age-associated tendon degeneration. Furthermore, this model system can be used in the future to identify cellular pathways involved in aging which alter the response of tenocytes to loading, and to identify anti-aging therapies which may be more effective in preventing load-induced tendon damage in aged populations.

项目总结 这个项目的长期目标是了解与年龄相关的生物变化的负面影响。 肌腱机械感觉和细胞外基质重塑。这个应用程序列出了一种策略，以 从力学上理解增加的压缩载荷环境对 肌腱功能，特别是与年龄相关的肩袖退变有关。中环 提出的假说是慢性炎症环境等与年龄有关 腱细胞突起的变化，合并由于不良的压缩负荷增加 姿势和肌肉结构，可能会导致肌腱退化。我们将首先利用我们的体外培养 模型与培养箱内的可控加载生物反应器一起创建压缩诱导 肌腱移植中的肌腱损伤。具体地说，我们正在建造首个此类双轴 肌腱植块组织机械加载生物反应器同时施加拉伸和 对试件进行压缩加载。使用这个生物反应器，我们将建立压缩模型- 由不同的加载时间(急性和慢性)和最大应变水平(低)引起的损伤 和高)。然后我们将使用这些模型来分离自然衰老和 炎症在组织损伤的发展过程中起作用。本申请中概述的项目结合了 基础基础研究的重要性与翻译面向未来的诊断和 早期肌腱退变的治疗。如果成功，这项工作将完全脱钩 炎症和机械负荷对年龄相关性肌腱退变的影响。 此外，这个模型系统可以在未来用于识别参与的细胞通路 改变肌腱细胞对负荷的反应的老化，并确定可以 在老年人群中预防负荷性肌腱损伤更有效。

项目成果

Earlier proteoglycan turnover promotes higher efficiency matrix remodeling in MRL/MpJ tendons.

较早的蛋白多糖周转可促进 MRL/MpJ 肌腱中更高效率的基质重塑。

• DOI: 10.1002/jor.25542
• 发表时间: 2023
• 期刊: Journal of orthopaedic research : official publication of the Orthopaedic Research Society
• 作者: Aggouras,AnthonyN;Connizzo,BrianneK
• 通讯作者: Connizzo,BrianneK