PROGRAM PROJECT GRANT

描述(由申请人提供)：基本假设 计划项目是腰椎间盘退变对低血压的贡献 背部疼痛和第二个假设是退行性变的过程可以是 被阻止的、迟缓的或修复的。我们的前提是无论是生物学的还是 生物力学因素参与了椎间盘退变的发病机制。这个 因此，计划项目同时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 通过探索不同的诊断方法， 阻止、延缓或修复退化过程，我们最终会减少 社会上的腰背痛问题。本计划所采用的方法 项目的目的是解决(1)诊断技术，通过这些技术， 退行性改变可在活体内评估；(2)机械因素 促进退行性变的发生；(3)生化 与椎间盘退变一起发生的改变；(4)减缓、逆转或 修复退化过程。该计划项目将使用 有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I将在活体内研究腰椎节段性运动 正常志愿者和椎弓根性腰痛患者。项目2将查看 应用有限元方法研究腰椎间盘损伤与重复负荷的关系 具有实验验证的单元模型。项目3将决定如何 盘结构和成分的变化与盘的变化相关 来自NP和AF的细胞的代谢并将使用体外培养模型来 研究退化过程和特定生长因子的能力 推进修缮。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对基质的影响 将生长因子转移到椎间盘细胞。在结束时， 计划期间，我们将拥有：(1)新的诊断技术，以更好地评估 临床上椎间盘退变对关节盘的力学影响 腰间盘。(2)对重复的影响有更好的理解 加载到椎间盘的机械完整性上，而这 信息可用于确定适当的受试者进行治疗。(3) 关于腰椎间盘退变与腰椎退变之间关系的认识 间盘细胞外基质的代谢以及 视盘细胞特定基因表达的改变。这将是 为生物化学或分子治疗方法提供平台 腰椎间盘退变。(4)关于替代方法的知识 根据退变程度预防、延缓或修复退变 退化。每个项目都高度融合在一起， 由生物力学、生物化学和管理核心支持。

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.