Intervertebral Disc Response to Cyclic Loading in Vivo

描述：这项拨款建议是为了响应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的子弹。这笔赠款汇集了哥伦比亚大学生物医学工程和整形外科系的一个多学科研究团队，以开发一种动物模型，该模型可用于建立临界阈值负载水平，在该阈值负载水平下，观察生理条件下循环加载下的椎间盘(IVD)的退变变化。 在工业化国家，职业暴露(例如，过度紧张、高重复负荷、全身振动)被普遍认为是下腰痛报告的重要原因。在美国，背部和脊柱问题是15岁及以上因振动暴露导致腰痛的第二大致残原因，据估计，振动暴露每年造成800亿美元的损失。 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)和椎骨的形态变化，类似于人类退行性腰椎间盘疾病。在这些模型中，PIN仪器化的小鼠和大鼠尾巴对静态加载或停用对椎间盘退变的影响有重要的洞察力。然而，显然还没有发表的研究使用这样的模型来研究体内IVD的应用循环负荷。为了解决脊柱研究中的这一明显差距，我们建议采用共同研究人员之一郭协力(Xe Guo)目前使用的活体大鼠尾巴模型来研究松质骨适应，以研究负荷诱导的IVD变化。在该模型中，通过加载到植入相邻椎体的外科钉上，可以将明确的加载方案(静态或随时间变化)应用于特定的椎体及其邻近的椎间盘。 为了隔离联合载荷条件对IVD响应的影响，我们提出了一些特定的假设和特定的目标来检验我们的全局假设，即存在一个可以安全地维持IVD正常功能和特性的载荷大小和频率范围。超出这一范围，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(硬度和弹性系数)的降低以及聚集素、I型和II型胶原以及软骨低聚蛋白(COMP)表达和水平的改变。

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).