Intervertebral Disc Response to Cyclic Loading in Vivo

椎间盘对体内循环负荷的反应

• 批准号: 6849394
• 负责人: Clark T. Hung
• 金额: $ 3.77万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-26 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6849394
• 关键词: SDS polyacrylamide gel electrophoresis; backache; biomechanics; charge coupled device camera; collagen; confocal scanning microscopy; disease /disorder model; extracellular matrix proteins; gene expression; histology; immunocytochemistry; intervertebral disk; laboratory rat; mechanical pressure; mechanical stress; messenger RNA; model design /development; polymerase chain reaction; serum; skeletal stress; spine disorder

DESCRIPTION: This grant proposal has been submitted in response to RFA-OH-02-004: Musculoskeletal Disorders: Prevention and Treatment, falling under the Biomechanical and Mechanobiology Research bullet. This grant brings together a multidisciplinary research team in the Departments of Biomedical Engineering and Orthopaedic Surgery at Columbia University to develop an animal model that can be used to establish the critical threshold loading level at which degenerative changes are observed in intervertebral discs (IVDs) subjected to cyclic loading under physiologic conditions. Occupational exposures (e.g., overstressed, high repetitive loading, whole body vibration) are generally accepted as an important cause of low back pain reports in industrialized countries. In the United States, back and spine problems represent the second greatest leading cause of disability among persons aged 15 years and older with low back pain from vibration exposure estimated to cost $80 billion annually. To better understand the impact of biomechanical factors on the etiology of disc degeneration, various animal models have introduced mechanical interventions on the spine or tail. These mechanical interventions cause morphologic changes in the intervertebral disc (IVD) and vertebrae similar to degenerative disc disease in humans. Amongst these models, pin instrumented mouse and rat tails have permitted significant insights to the effect of static loading or disuse on disc degeneration. There are,however, apparently no published studies using such models to study applied cyclic loading of the IVD in vivo. To address this apparent gap in spine research, we propose to adapt the in vivo rat tail model currently used by one of the co-Investigators (XE Guo) to study trabecular bone adaptation, to study loading-induced changes in the IVD. In this model, a well-defined loading regiment (static or temporally varying) can be applied to a specific vertebra and its adjacent discs via loading to surgical pins implanted in the neighboring vertebrae. With the ultimate goal of isolating the influence of joint-loading conditions on the response of the IVD, we set forth a number of specific hypotheses and specific aims test our global hypothesis that there exists a range of loading magnitudes and frequencies that will safely maintain normal function and properties of the IVD. Outside of this range, non-physiologic compressive loading (overloading, high frequency, or static loading) of the IVD leads to disc degeneration as measured by decreased material properties (stiffness and modulus) and alterations to expression and levels of aggrecan, type I and II collagen, and cartilage oligomeric protein (COMP).

描述：该赠款提案是针对RFA-OH-02-004提交的：肌肉骨骼疾病：预防和治疗，属于生物力学和机械生物学研究子弹。 该赠款汇集了哥伦比亚大学生物医学工程和骨科手术部门的多学科研究团队，以开发一种动物模型，该模型可用于确定在生理学条件下经受过环状载荷的椎间盘盘（IVD）中观察到的关键阈值载荷水平，在该模型中会观察到退行性变化。 职业暴露（例如，过度压力，高度重复的负荷，全身振动）通常被视为工业化国家下腰痛报告的重要原因。 在美国，背部和脊柱问题代表了15岁及15岁以上残疾的第二大主要原因，其振动暴露估计为每年耗资800亿美元，腰痛。 为了更好地理解生物力学因素对椎间盘退化病因的影响，各种动物模型已经在脊柱或尾部引入了机械干预措施。 这些机械干预会导致椎间盘（IVD）和椎骨类似于人类的退行性椎间盘疾病的形态变化。 在这些模型中，PIN仪器的小鼠和大鼠尾巴允许对静态负载或废除椎间盘变性的影响有重大见解。 但是，显然没有使用此类模型来研究体内IVD的循环载荷的发表研究。 为了解决脊柱研究中的这一明显差距，我们建议适应一位共同投资剂（XE Guo）目前使用的体内大鼠尾巴模型（XE Guo）来研究小梁骨适应，以研究IVD的负载诱导的变化。在此模型中，可以通过将植入相邻椎骨植入的外科销量加载到植入的手术销，将定义明确的加载团（静态或时间变化）应用于特定的椎骨及其相邻盘。 为了隔离联合加载条件对IVD响应的影响的最终目标，我们设定了许多特定的假设，并且特定的目的测试了我们的全球假设，即存在一系列的负载大小和频率，这些假设将安全地维持IVD的正常功能和性质。 在此范围之外，IVD的非生理压缩负荷（过载，高频或静态负载）导致盘式退化，通过降低材料特性（刚度和模量）以及对Aggrecan，A型和II型胶原蛋白胶原的表达和水平的变化，以及软骨寡头蛋白质（组合）。