Intervertebral disc plasticity in response to mechanical and biological perturbations

响应机械和生物扰动的椎间盘可塑性

• 批准号: RGPIN-2020-04723
• 负责人: Gregory, Diane
• 金额: $ 3.42万
• 依托单位: Wilfrid Laurier University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=757851
• 关键词: Intervertebral; disc; plasticity; response; mechanical

Musculoskeletal tissues are constantly exposed to various types of stimuli and must respond adequately through remodelling to maintain homeostasis. The long-term goal of my research program is to advance our understanding of how the spine responds to mechanical and biological stimuli and how this ultimately affects biomechanics. Proposed experiments aim to investigate the effect of both mechanical and specifically inflammatory stimuli on the biomechanical properties at both the cellular and whole intervertebral disc level in the spine. It is anticipated that an interdependent relationship exists where either type of stimulant will perturb both biomechanical and biological equilibrium in the spine, thereby altering tissue structure (through remodelling) and function (mechanical integrity). Cells extracted from rat intervertebral discs will be embedded in collagen scaffolds which will then be exposed to mechanical and/or inflammatory stimulation. Following exposure, changes to the mechanical properties of the collagen scaffold (and therefore evidence of remodelling) as well as expression of tissue remodelling genes will be examined. Similarly, at the tissue level, whole discs will be exposed to similar stimuli and biomechanical properties of the intact discs will be quantified in order to discern remodelling in response to the stimulation. Last, exploratory experiments are aimed at uncovering the mechanistic pathways responsible for changes in disc biomechanics in response to both mechanical and inflammatory stimulation; this will be done by manipulating these pathways via receptor inhibition or altered regulation of tissue remodelling genes. This research will therefore provide a new understanding of the important pathways and processes involved in altering the mechanical properties of the intervertebral disc. Currently, minimal research is focused on the combination of these attributes making the proposed work novel in furthering our understanding of intervertebral disc function. Findings from this body of work also have the potential to assist in our understanding of disc pathologies, a prevalent issue among Canadian and significant source of disability worldwide.

肌肉骨骼组织不断地暴露在各种类型的刺激下，必须通过重塑做出充分的反应，以维持体内平衡。我的研究计划的长期目标是促进我们对脊柱对机械和生物刺激的反应以及这最终如何影响生物力学的理解。建议的实验旨在研究机械刺激和特别是炎症刺激对脊柱细胞和整个椎间盘水平的生物力学特性的影响。预计存在一种相互依赖的关系，其中任何一种刺激剂都会扰乱脊柱的生物力学和生物平衡，从而改变组织结构(通过重塑)和功能(机械完整性)。从大鼠椎间盘中提取的细胞将被嵌入到胶原支架中，然后暴露在机械和/或炎症刺激下。暴露后，将检查胶原支架的机械性能的变化(因此也是重塑的证据)以及组织重塑基因的表达。类似地，在组织水平上，整个椎间盘将暴露在类似的刺激下，完整的椎间盘的生物力学特性将被量化，以便识别对刺激的响应的重塑。最后，探索性实验的目的是揭示在机械刺激和炎症刺激下导致椎间盘生物力学变化的机械途径；这将通过受体抑制或组织重塑基因的改变调节来操纵这些途径。因此，这项研究将对改变椎间盘力学性质的重要途径和过程提供新的理解。目前，极少的研究集中在这些属性的组合上，使拟议的工作在加深我们对椎间盘功能的理解方面具有新颖性。这项工作的发现也有可能有助于我们对椎间盘病理的理解，这是加拿大人普遍存在的问题，也是全球残疾的重要来源。