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。特定的组织包括肌腱、韧带、骨骼和独特设计的椎间盘(IVD)。这些组织，以及肌肉和神经，必须协同工作，为脊柱提供灵活性和支撑力。这些结构中的任何一种损伤都可能导致脊柱损伤和功能障碍，并可能导致下腰痛。80%的加拿大人在生活中的某个时候会经历下腰痛，这种疼痛可能会使人极度虚弱，影响到生活的方方面面。该建议旨在通过研究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)以及这两种特性是如何紧密联系起来的，来揭示IVD可塑性的基本机制。作为本提案的一部分进行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已经受损，这对随后的组织破坏有何影响？3)IVD的各个组成部分如何适应高要求的场景，以防止损害？哪些蛋白质和细胞对这种适应有贡献？重点将放在了解机械暴露和生物反应之间的联系，以便认识到这一独特结构的形式和功能之间的联系。此外，将对IVD或IVD变性的自然进行性崩溃进行广泛检查，以获得关于这种常见但往往使人虚弱的随年龄增长的疾病的进一步信息。这项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，以便了解脊柱是如何适应或受伤的。

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.