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：本拨款提案是为了响应 RFA-OH-02-004：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项目而提交的。 这笔赠款汇集了哥伦比亚大学生物医学工程和骨科外科系的多学科研究团队，开发一种动物模型，可用于建立临界阈值负荷水平，在该水平下观察椎间盘（IVD）的退行性变化生理条件下的循环负荷。 在工业化国家中，职业暴露（例如压力过大、高重复负荷、全身振动）被普遍认为是导致腰痛的重要原因。 在美国，背部和脊柱问题是 15 岁及以上人群残疾的第二大主要原因，由于振动暴露导致腰痛，每年造成的损失估计达 800 亿美元。 为了更好地了解生物力学因素对椎间盘退变病因的影响，各种动物模型引入了对脊柱或尾部的机械干预。 这些机械干预会导致椎间盘（IVD）和椎骨的形态变化，类似于人类的退行性椎间盘疾病。 在这些模型中，使用针仪器的小鼠和大鼠尾巴可以显着了解静态负载或废弃对椎间盘退变的影响。 然而，显然没有已发表的研究使用此类模型来研究 IVD 体内应用的循环负载。 为了解决脊柱研究中的这一明显差距，我们建议采用目前由一位共同研究者（XE郭）用于研究小梁骨适应的体内鼠尾模型，以研究负载引起的 IVD 变化。在此模型中，可以通过加载到植入相邻椎骨中的手术针，将明确定义的加载团（静态或随时间变化）应用于特定椎骨及其相邻椎间盘。 最终目标是隔离联合载荷条件对 IVD 响应的影响，我们提出了许多具体假设和具体目标来测试我们的总体假设，即存在一系列可以安全维持正常的载荷大小和频率。 IVD 的功能和特性。 在此范围之外，IVD 的非生理性压缩负荷（过载、高频或静态负荷）会导致椎间盘退变，具体表现为材料特性（刚度和模量）下降以及聚集蛋白聚糖、I 型和 I 型聚集蛋白聚糖的表达和水平的改变。 II 胶原蛋白和软骨寡聚蛋白 (COMP)。