PROGRAM PROJECT GRANT

描述（由申请人提供）： 计划项目是，椎间盘退变有助于低 第二个假设是，退化的过程可以是 预防、延缓或修复。我们的前提是，生物学和 生物力学因素有助于椎间盘退变的发病机制。的 因此，该计划项目涉及生物力学和生物学 椎间盘退变的症状通过提高我们对 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 社会上的腰痛问题。本方案采取的办法 该项目旨在解决（1）诊断技术， 可以在体内评估退行性变化;（2）机械因素 有助于椎间盘退行性变化的发展;（3）生物化学 椎间盘退变发生的变化;（4）减缓、逆转或 修复退化过程该计划项目将使用 多学科的方法，有骨科成员的参与， 外科学、放射学、生物力学、解剖学、生物化学和分子生物学。 项目一将研究在体内节段性脊柱运动的腰椎， 正常志愿者和椎间盘源性腰痛患者。项目2将着眼于 应用有限元法探讨椎间盘损伤与重复负荷的关系 元件模型与实验验证。项目3将决定如何 椎间盘结构和组成的变化与 来自NP和AF的细胞的代谢，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的基因 将生长因子转移到椎间盘细胞。结束时 计划期间，我们将有：（1）新的诊断技术，以更好地评估 在临床上，椎间盘退变对 椎间盘(2)更好地理解重复性 对椎间盘的机械完整性施加载荷， 信息可用于识别适当的治疗对象。（三） 关于椎间盘退变与椎间盘内 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 为生物化学或分子治疗方法提供平台， 椎间盘退变(4)关于替代方法的知识 预防、延缓或修复椎间盘退变， 退化每一个项目都是高度融合的， 由生物力学，生物化学和行政核心支持。

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.