PROGRAM PROJECT GRANT

计划项目拨款

• 批准号: 6944047
• 负责人: Gunnar BJ Andersson
• 金额: $ 148.26万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6944047
• 关键词: intervertebral disk; spinal disk injury; spine disorder

DESCRIPTION (provided by applicant): The underlying primary hypothesis of the Program project is that intervertebral disc degeneration contributes to low back pain and a second hypothesis is that the process of degeneration can be prevented, retarded or repaired. Our premise is that both biological and biomechanical factors contribute to the pathogenesis of disc degeneration. The Program project therefore, addresses both the biomechanical and biological aspects of disc degeneration. By improving our understanding of the degenerative process and by exploring different approaches to diagnose, prevent, retard or repair the degenerative process, we will ultimately decrease the problem of low back pain in society. The approach taken in this Program project is to address (1) diagnostic techniques by which the impact of the degenerative changes can be assessed in vivo; (2) mechanical factors contributing to the development of degenerative disc changes; (3) biochemical changes occurring with disc degeneration and; (4) methods to slow, reverse or repair the degenerative process. The Program project will be completed using a multi-disciplinary approach with the participation of members from orthopedic surgery, radiology, biomechanics, anatomy, biochemistry, and molecular biology. Project I will study in vivo segmental spine motion of the lumbar spine in normal volunteers and discogenic low-back-pain patients. Project 2 will look at the relationship between disc injury and repetitive loading using finite element models with experimental validation. Project 3 will determine how changes in disc structure and composition correlate with changes in the metabolism of cells from the NP and AF and will use culture models in vitro to study degenerative processes and the ability of specific growth factors to promote repair. Project 4 will study regeneration of the intervertebral disc matrix by assessing the effects of growth factors and gene gun mediated gene transfer of growth factors to intervertebral disc cells. At the end of the program period we will have: (1) New diagnostic techniques to better assess clinically the mechanical consequences of disc degeneration on the intervertebral disc. (2) An improved understanding of the effects of repetitive loading on the mechanical integrity of the intervertebral disc, and this information can be used to identify appropriate subjects for treatment. (3) Knowledge about the relationship between disc degeneration and changes in the metabolism of the extracellular matrix of the intervertebral disc as well as alterations in the expression of specific genes by disc cells. This will provide a platform for biochemical or molecular therapeutic approaches for intervertebral disc degeneration. (4) Knowledge about alternative approaches to prevent, retard or repair disc degeneration based on the degree of degeneration. Each of the projects are highly integrated with each other and supported by Biomechanics, Biochemistry and Administrative Cores.

描述（由申请人提供）：基本的主要假设 计划项目是椎间盘退变导致低 背痛，第二个假设是退化过程可以是 预防、阻碍或修复。我们的前提是生物和 生物力学因素导致椎间盘退变的发病机制。这 因此，计划项目涉及生物力学和生物学 椎间盘退变的各个方面。通过提高我们对 退化过程并通过探索不同的诊断方法， 预防、延缓或修复退化过程，我们最终将减少 社会上腰痛的问题。本计划采取的方法 项目的目的是解决（1）诊断技术，通过该技术， 可以在体内评估退行性变化； (2)机械因素 促进退行性椎间盘变化的发展； (3)生化 因椎间盘退变而发生的变化； (4) 减速、倒转或 修复退化过程。该计划项目将使用 骨科成员参与的多学科方法 外科、放射学、生物力学、解剖学、生物化学和分子生物学。 项目一将研究腰椎的体内节段运动 正常志愿者和椎间盘源性腰痛患者。项目2将着眼于 使用有限元分析椎间盘损伤与重复负荷之间的关系 经过实验验证的元素模型。项目 3 将确定如何 椎间盘结构和成分的变化与椎间盘的变化相关 NP 和 AF 细胞的代谢，并将使用体外培养模型 研究退化过程和特定生长因子的能力 促进修复。项目4将研究椎间盘的再生 通过评估生长因子和基因枪介导基因的影响来构建矩阵 将生长因子转移至椎间盘细胞。结束时 计划期间我们将拥有：（1）新的诊断技术，以更好地评估 临床上椎间盘退变的机械后果 椎间盘。 (2) 加深对重复性影响的理解 对椎间盘的机械完整性造成负荷，这 信息可用于确定适当的治疗对象。 (3) 了解椎间盘退变与椎间盘变化之间的关系 椎间盘细胞外基质的代谢以及 椎间盘细胞特定基因表达的改变。这将 为生化或分子治疗方法提供平台 椎间盘退变。 (4)了解替代方法 根据椎间盘退变的程度来预防、延缓或修复 退化。每个项目都高度集成， 由生物力学、生物化学和行政核心支持。