Integrating mechanics and physiology to define form and function of the intervertebral disc

脊柱是一个复杂的复合结构，由各种生物组织错综复杂地组成。特定组织包括肌腱、韧带、骨骼和独特设计的椎间盘（IVD）。这些组织，连同肌肉和神经，必须协同工作以提供脊柱的灵活性和支撑力。这些结构的任何损伤都可能导致脊柱损伤和功能障碍，并可能导致腰痛。80%的加拿大人在生活的某个阶段都经历过腰痛，它会对生活的各个方面造成极大的影响。本研究旨在通过研究IVD的形态（细胞外基质、蛋白质组成、细胞含量）和功能（机械性能、抗损伤能力）以及这两种特性之间的密切联系，揭示IVD可塑性的基本机制。作为本提案一部分的研究将解决的具体问题包括：1)IVD是如何受损的？2)如果IVD已经损坏，这对随后的组织破坏有何影响？3) IVD的各个组件如何适应高要求的场景以防止损坏？哪些蛋白质和细胞促成了这种适应？重点将放在了解机械暴露和IVD生物反应之间的联系，以便认识到这种独特结构的形式和功能之间的联系。此外，将广泛检查IVD的自然进行性分解或IVD变性，以获得有关这种常见但经常使人衰弱的随年龄增长而发生的疾病的进一步信息。本研究的基本目标是确定脊柱的机械和生理环境之间的复杂关系，以了解脊柱如何适应或成为损伤。

The spine is a complex composite structure intricately comprised of various biological tissues. Specific tissues include tendons, ligaments, bone, and the uniquely designed intervertebral disc (IVD). These tissues, along with muscles and nerves, must work together to provide both flexibility and support in the spine. Damage to any of these structures can result in impairment and dysfunction of the spine and could lead to low back pain. Low back pain is experienced by 80% of the Canadian population at some point in their lives and can be extremely debilitating affecting all aspects of life. This proposal aims to uncover the basic mechanisms of IVD plasticity by examining its form (extracellular matrix, protein composition, cellular content) and function (mechanical properties, ability to resist damage) and how these two properties are intimately linked. Specific questions addressed by the research conducted as part of this proposal will include 1) How does the IVD become damaged? 2) If the IVD is already damaged, how does this affect subsequent tissue breakdown? 3) How do individual components of the IVD adapt to high demanding scenarios to prevent damage? What proteins and cells contribute to this adaptation? Emphasis will be placed on understanding links between mechanical exposures and biological responses in the IVD in order to recognize the association between form and function of this unique structure. Further, natural progressive breakdown of the IVD, or IVD degeneration, will be extensively examined in order to gain further information about this common, yet often debilitating, disorder that occurs with age. The fundamental goal of this research is to determine the intricate relationship between the mechanical and physiological environment of the spine in order to understand how the spine adapts or becomes injured.