Exercise-induced recovery of intervertebral disc health

运动引起的椎间盘健康恢复

• 批准号: 10039220
• 负责人: John Martin
• 金额: $ 8.36万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10039220
• 关键词: Adult; Affect; Age; Anabolism; Anatomy; Animal Model; Animals; Back Pain; Benchmarking; Biological Assay; Blood Vessels; Cartilage; Cell Survival; Cell membrane; Cells; Cellular biology; Characteristics; Clinical; Control Groups; Convection; Devices; Diagnosis; Diagnostic radiologic examination; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Dose; Elderly; Excision; Exercise; Frequencies; Future; GLUT-1 protein; Geometry; Glucose; Glucose Transporter; Goals; Health; Homeostasis; Human; Image; Intervertebral disc structure; Liquid substance; Literature; Low Back Pain; Magnetic Resonance Imaging; Measures; Membrane Transport Proteins; Modeling; Nutrient; Operative Surgical Procedures; Oxygen; PET/CT scan; Pain; Patients; Peripheral; Porosity; Process; Protocols documentation; Rattus; Recovery; Running; Speed; Structure; System; Testing; Training; Translating; Translations; Vertebral column; Work; age related; aged; clinical implementation; disability; disc regeneration; exercise intensity; exercise program; experience; fluorodeoxyglucose; glucose uptake; grasp; imaging modality; improved; in vivo; instrument; intervertebral disk degeneration; non-invasive imaging; pain outcome; pain sensitivity; peripheral pain; programs; protein expression; radiotracer; regenerative; response; sample fixation; solute; spine bone structure; translational pipeline; treadmill; wasting; young adult

Project Summary The lumbar intervertebral discs naturally degenerate with age and are implicated in low back pain, the world’s leading cause of disability. Because the discs are avascular, cells residing in the central disc are up to 6-8 mm from the nearest blood vessel in adults. To maintain homeostasis, disc cells rely on diffusion and convection between the discs and adjacent vertebrae for nutrient transport and waste removal. When transport is compromised, local glucose and oxygen concentrations decrease, pH decreases, and cell viability and matrix turnover are impacted. Currently, there are no clinical strategies to intervene in age-related degeneration, but improving fluid transport may be one strategy to slow or reverse the process. Previous work in animals instrumented with external loading devices suggests that dynamic loading increases the rate of solutes transported into the discs and causes disc anabolism. One way to induce loading in vivo is through exercise and running exercise was recently related to improved disc health in animals and humans. Still, it is not clear how in vivo loading modulates fluid and nutrient transport and which exercise protocols induce the appropriate dynamic loads. Exercise dosing is likely an important factor, however there is a “complete lack of studies in the exercise and pain literature testing multiple doses of exercise in a single patient (or control) group”. The objective of this work is to identify factors that affect fluid and nutrient transport and implement an exercise protocol that optimizes transport for disc regeneration. In Aim 1, rats of young, adult, and advanced ages will be evaluated for differences in exercise-induced disc fluid transport and factors related to fluid transport (cartilage endplate porosity, disc deformations during activity) as well as exercise-induced cellular glucose uptake and factors that affect glucose uptake (cell membrane transporters). In Aim 2, rats of young and advanced ages will be evaluated while executing one of 6 8-week treadmill programs of varying intensity for changes in disc function, composition, structure, and pain. In Aim 3, rats with surgically-induced degeneration will be evaluated while executing an 8-week treadmill program for changes in disc function, composition, structure, and pain. There will be two control groups to determine the specific impact of exercise-induced loading. My goal is to develop a translational pipeline to test and iterate disc regeneration strategies in animals and seamlessly import those into humans. The results from this study will identify exercise protocols that maximize disc fluid transport, glucose uptake, and disc health and can be translated to humans for disc regeneration.

项目摘要 腰间盘随着年龄的增长而自然退化，并与下腰痛有关， 是世界上导致残疾的主要原因。因为椎间盘是无血管的，所以驻留在中央椎间盘中的细胞高达 成人距最近血管6~8 mm。为了维持动态平衡，视盘细胞依靠扩散和 椎间盘和相邻椎骨之间的对流，用于营养物质的运输和废物的清除。当运输时 受损，局部葡萄糖和氧气浓度下降，pH下降，细胞活力和 矩阵周转受到影响。目前，还没有干预年龄相关疾病的临床策略。 但改善液体运输可能是减缓或逆转这一过程的一种策略。 之前在装有外部加载装置的动物身上所做的工作表明，动态加载 增加溶质进入圆盘的速度，并导致圆盘合成代谢。一种诱导负荷的方法 在活体内通过运动和跑步运动最近被认为与改善动物的椎间盘健康有关 人类。然而，目前还不清楚体内负荷如何调节液体和营养物质的运输，以及哪些运动 协议会产生适当的动态负载。运动量可能是一个重要因素，但也有 运动和疼痛文献中完全缺乏对一次多剂量运动进行测试的研究 患者(或对照)组。这项工作的目的是确定影响液体和营养的因素 运输和实施锻炼方案，以优化光盘再生的运输。 在目标1中，年轻、成年和高龄的大鼠将被评估运动诱导的差异。 关节盘液体传输及其相关因素(软骨终板孔隙率、关节盘变形 活动)以及运动诱导的细胞葡萄糖摄取和影响葡萄糖摄取的因素(细胞 膜转运蛋白)。在目标2中，将评估年轻和高龄大鼠在执行以下操作之一时的情况 6个为期8周的不同强度的跑步机计划，以观察椎间盘功能、成分、结构和疼痛的变化。 在目标3中，将在执行为期8周的跑步机时对手术诱导的变性大鼠进行评估。 改变椎间盘功能、成分、结构和疼痛的程序。将有两个控制组 确定运动负荷的具体影响。 我的目标是开发一个翻译流水线来测试和迭代光盘再生策略 并无缝地将这些动物输入人类体内。这项研究的结果将确定锻炼 最大限度地提高间盘液体运输、葡萄糖摄取和间盘健康的方案，并可以翻译成人类 用于光盘再生。