Program Project grant

计划 项目补助金

• 批准号: 7673776
• 负责人: Gunnar BJ Andersson
• 金额: $ 123.9万
• 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 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7673776
• 关键词: Program; Project; grant

DESCRIPTION (Provided by the applicant) The underlying primary hypothesis, that intervertebral disc degeneration contributes to low back pain, and a second hypothesis, that the process of degeneration can be prevented, retarded or repaired, of this renewal Program Project Grant remain. The four projects of the ongoing Program Project Grant form the basis for this competitive renewal application and have achieved an improved understanding of the biomechanical and metabolic factors involved in intervertebral disc degeneration. Project 1 developed a new precise and reproducible non-invasive 3-D analysis method of measuring segmental motion of the lumbar spine. Project 2 developed and validated a finite element model, which includes fluid flow and the poro-elastic behavior of the intervertebral disc. Project 3 identified biochemical changes in collagens, proteoglycans, and matrixdegrading enzymes in the intervertebral disc that are associated with aging and/or tissue degeneration. Project 4 developed an annular puncture rabbit model of acute or sub-acute intervertebral disc degeneration and showed that the injection of growth factor up-regulates matrix synthesis with restoration of disc height. In this renewal proposal, we have designed experiments that are mechanistic, hypothesis-driven and potentially translational to further advance our understanding of the biomechanical and biological factors associated with intervertebral disc degeneration. Project 1 will measure kinematic hypermobility in torsion and flexionextension in vivo and correlate those data with low back pain symptoms. Factors of prognostic importance to the progression of disc and facet joint degeneration and symptoms will be identified. Project 2 will focus on developing a finite element model that more closely corresponds to a degenerative disc and will study its response to repetitive loading. Project 3 will determine the mechanism of action and interplay between growth factors, cytokines and different regulatory molecules in disc tissue homeostasis and their potential use in promoting disc tissue repair. Project 4 will determine if disc degeneration can be delayed or reversed by manipulating the balance between anabolic and catabolic pathways and if compromised nutrient transport through the endplate limits cell-mediated disc repair induced by the application of a growth factor. This Program Project will result in major progress that will directly translate into relief for so many individuals suffering from low back pain that is associated with intervertebral disc and facet joint degeneration.

描述(由申请人提供) 基本的基本假设，即椎间盘退变导致下腰痛，以及第二个假设，即退变过程可以预防、延缓或修复，这一更新计划项目赠款保留了下来。正在进行的计划项目赠款的四个项目构成了这一竞争性续签申请的基础，并实现了对涉及椎间盘退变的生物力学和代谢因素的更好理解。项目1开发了一种新的精确和可重复性的非侵入性三维分析方法，用于测量腰椎的节段性运动。项目2开发并验证了一个有限元模型，该模型包括流体流动和椎间盘的多孔弹性行为。项目3确定了与衰老和/或组织退化有关的椎间盘中胶原蛋白、蛋白多糖和基质降解酶的生化变化。项目4建立了急性或亚急性椎间盘退变的环状穿刺兔模型，并表明注射生长因子可上调基质合成，恢复椎间盘高度。在这个更新方案中，我们设计了机械性的、假设驱动的和潜在的平移的实验，以进一步加深我们对与椎间盘退变相关的生物力学和生物学因素的理解。项目1将在体内测量扭转和屈曲伸展时的运动性高机动性，并将这些数据与下腰痛症状相关联。对椎间盘和小关节退变的进展和症状具有重要预后意义的因素将被确定。项目2将专注于开发一个更接近于退变椎间盘的有限元模型，并将研究其对重复加载的反应。项目3将确定生长因子、细胞因子和不同调节分子在椎间盘组织稳态中的作用和相互作用机制，以及它们在促进椎间盘组织修复方面的潜在应用。项目4将确定是否可以通过控制合成代谢和分解代谢途径之间的平衡来延缓或逆转椎间盘退变，以及通过终板的营养运输受损是否限制了应用生长因子诱导的细胞介导的椎间盘修复。这一计划项目将带来重大进展，将直接转化为缓解如此多与腰椎间盘和小关节退变相关的腰痛患者的痛苦。