Program Project grant

描述（由申请人提供） 基本的主要假设，即椎间盘退变导致腰痛，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仍然存在。正在进行的计划项目资助的四个项目构成了这种竞争性更新申请的基础，并提高了对椎间盘退变所涉及的生物力学和代谢因素的理解。项目1开发了一种新的测量腰椎节段运动的精确和可重复的非侵入性3-D分析方法。项目2开发并验证了有限元模型，其中包括流体流动和椎间盘的多孔弹性行为。项目3确定了椎间盘中胶原蛋白、蛋白多糖和基质降解酶的生化变化，这些变化与衰老和/或组织变性有关。项目4开发了急性或亚急性椎间盘退变的环形穿刺兔模型，并显示注射生长因子上调基质合成，恢复椎间盘高度。在这项更新提案中，我们设计了机械的、假设驱动的和潜在转化的实验，以进一步推进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将测量在体扭转和屈伸的运动学过度活动，并将这些数据与腰痛症状相关联。将确定对椎间盘和小关节退变和症状进展具有重要预后意义的因素。项目2将专注于开发一个更接近退行性椎间盘的有限元模型，并将研究其对重复载荷的反应。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机制和相互作用，以及它们在促进椎间盘组织修复中的潜在用途。项目4将确定椎间盘退变是否可以通过操纵合成代谢和分解代谢途径之间的平衡来延迟或逆转，以及通过终板的营养运输是否会限制生长因子应用诱导的细胞介导的椎间盘修复。该计划项目将导致重大进展，这将直接转化为缓解许多患有与椎间盘和小关节退变相关的腰痛的人。

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.