PATHOLOGY OF INTERVERTEBRAL DISC DISEASE

椎间盘疾病的病理学

• 批准号: 5206254
• 负责人: ROLAND W MOSKOWITZ
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5206254
• 关键词: biological models; biomechanics; chondrocytes; crosslink; fluorescent dye /probe; glycosylation; high performance liquid chromatography; histopathology; human tissue; image processing; intervertebral disk; laboratory rat; mechanical stress; microradiography; pathologic bone resorption; pathologic process; proteoglycan; spinal cord imaging /visualization; spine disorder

Although intervertebral disc degeneration is a leading cause of musculoskeletal disability leading to pain, work loss and high cost to industry, a clear understanding of mechanisms of disease pathogenesis and specific therapeutic approaches is still lacking. Few studies have been directed toward parallel and sequential assessment of biochemical, biomechanical and anatomic responses. The proposed investigations in a well-defined model are designed to utilize biochemical, biomechanical, histopathologic and histomorphometric methods to define the pathophysiologic processes taking place during intervertebral disc degeneration. The specific objectives of the studies are designed to 1) determine whether biochemical and physicochemical changes in the intervertebral disc and vertebral bodies precede or follow alterations in joint biomechanics and structure. Correlative studies will utilize measurements of disc hydration and swelling pressure responses to assess physicochemical changes; and fixed charge density (FCD) measurements to assess proteoglycan alterations. Biomechanical assessment of disc alterations will be evaluated utilizing measurements of disc responses in bending and compression modes. 2) determine whether subchondral bone responses precede and initiate/contribute to alterations in the intervertebral disc. This question will be investigated utilizing both sequential fluorochrome labeling, and quantitative measurements of subchondral bone responses utilizing an automated image analysis system (Bioquant IV). 3) determine whether alterations in collagen cross-linking and/or non-enzymatic glycosylation play a major role in the disc degenerative process. In addition to assessing de novo responses of these biochemical parameters, the effect of variations in biomechanical stresses on the rate and degree of these responses will be investigated.

虽然椎间盘退变是导致椎间盘突出的主要原因 肌肉骨骼残疾导致疼痛、工作损失和高昂的治疗费用 行业，清楚地了解疾病发病机制和 目前仍缺乏具体的治疗方法。 很少有研究 针对生化的平行和连续评估， 生物力学和解剖学反应。 拟议的调查 明确定义的模型旨在利用生物化学、生物力学、 组织病理学和组织形态计量学方法来定义 椎间盘突出过程中发生的病理生理过程 退化。 研究的具体目标旨在：1) 确定是否发生生化和理化变化 椎间盘和椎体发生变化之前或之后 关节生物力学和结构。 相关研究将利用 测量椎间盘水合和肿胀压力反应以评估 物理化学变化；和固定电荷密度 (FCD) 测量 评估蛋白多糖的改变。 椎间盘生物力学评估 将利用椎间盘反应的测量来评估改变 弯曲和压缩模式。 2）判断是否有软骨下骨 反应先于并引发/促成改变 椎间盘。 这个问题将利用两者进行调查 连续荧光标记和定量测量 利用自动图像分析系统的软骨下骨反应 （生物定量IV）。 3) 确定胶原蛋白交联是否发生改变 和/或非酶糖基化在椎间盘中起主要作用 退化过程。 除了评估这些的从头反应 生化参数、生物力学应力变化的影响 将调查这些反应的速率和程度。