Intervertebral Disc Response to Cyclic Loading in Vivo

产品说明：本拨款申请是为了响应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。 这项资助汇集了哥伦比亚大学生物医学工程和矫形外科系的多学科研究团队，以开发一种动物模型，该模型可用于建立临界阈值负荷水平，在该阈值负荷水平下，在生理条件下接受循环负荷的椎间盘（IVD）中观察到退行性变化。 职业暴露（例如，过度紧张、高重复负荷、全身振动）通常被认为是工业化国家报告的腰痛的重要原因。 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，据估计，每年因振动引起的腰痛造成的损失为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，各种动物模型都在脊柱或尾部引入了机械干预。 这些机械干预导致椎间盘（IVD）和椎骨的形态学变化，类似于人类退行性椎间盘疾病。 在这些模型中，用针固定的小鼠和大鼠尾巴可以显著观察静态负荷或废用对椎间盘退变的影响。 然而，显然没有发表的研究使用这种模型来研究体内IVD施加的循环载荷。 为了解决脊柱研究中的这一明显差距，我们建议调整目前由合作研究者之一（XE Guo）用于研究骨小梁适应性的体内大鼠尾部模型，以研究IVD中负载诱导的变化。在该模型中，可以通过对植入相邻椎骨中的手术钉进行加载，将明确定义的加载方案（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，我们提出了一些具体假设，具体目标是测试我们的总体假设，即存在一系列载荷幅度和频率，可以安全地保持IVD的正常功能和特性。 在该范围之外，IVD的非生理压缩载荷（过载、高频或静态载荷）导致椎间盘退变，如通过降低的材料特性（刚度和模量）以及聚集蛋白聚糖、I型和II型胶原和软骨寡聚蛋白（COMP）的表达和水平的改变所测量的。

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).