Strain-Dependent Glucose Transport and Metabolism in Intervertebral Disc

椎间盘中应变依赖性葡萄糖转运和代谢

• 批准号: 7615889
• 负责人: Alicia R Jackson
• 金额: $ 2.84万
• 依托单位: UNIVERSITY OF MIAMI CORAL GABLES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2011-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7615889
• 关键词: Affect; Bathing; Biological; Cells; Consumption; Custom; Data; Development; Diffusion; Economics; Equation; Extracellular Matrix; Family suidae; Functional disorder; Glucose; Goals; Human; Human body; Intervertebral disc structure; Knowledge; Low Back Pain; Measures; Mechanics; Metabolic; Metabolism; Nutrient; Outcome Study; Partition Coefficient; Property; Signal Transduction; Specimen; Stimulus; Structure; Swelling; Testing; Theoretical model; Tissues; United States; Vertebral column; Water; design; glucose monitor; glucose transport; insight; intervertebral disk degeneration; nutrition; research study; response; solute; treatment strategy

DESCRIPTION (provided by applicant): Low back pain (LBP) is a major socio-economic concern in the US. While the exact cause of LBP is not clear, degeneration of the intervertebral discs (IVD) of the spine is believed to be the main origin. The IVD is the largest avascular structure in the human body, making transport of water and solutes in the discs an important mechanism of nutrition. Knowledge of transport and metabolic properties of important nutrients (e.g. glucose) is important in understanding pathophysiology involved in disc degeneration. Mechanical forces at the tissue level can affect physical signals at the cellular level and the way tissue remodeling changes physical signals through changes in tissue material properties and may also regulate cellular responses that may govern the initiation and progression of disc degeneration. Thus, determining changes in tissue properties as a result of mechanical strain is important in understanding the biological responses of IVD cells to force and other stimuli, and is therefore important in elucidating the etiologic factors involved in disc degeneration and LBP. The applicant's long-term goals are to (1) better understand the pathophysiology involved in the development of LBP; (2) further elucidate transport and metabolic properties in normal and degenerated IVD; and (3) develop new strategies for assessing and treating disc degeneration and LBP. The main objective of this proposal is to determine the effects of mechanical strain on glucose transport and metabolism in non-degenerated and degenerated human IVD tissues. In order to achieve this objective, the proposed plan is divided into three studies combining theoretical and experimental approaches. In Study #1, the strain-dependent glucose diffusivity in normal and degenerated human IVD tissues will be determined (Specific Aim #1) using a 1D unsteady state diffusion experiment and a custom designed diffusion cell. In Study #2, the strain-dependent partition coefficient of glucose in normal and degenerated human IVD tissues will be determined (Specific Aim #2) by measuring glucose concentrations within three baths equilibrated sequentially with tissue specimens under compressed and free-swelling conditions. In Study #3, the strain-dependent glucose consumption rate of porcine IVD cells will be determined (Specific Aim #3) by monitoring of glucose concentrations in bathing medium and using FEM analysis and theoretical curve-fitting with the Michaelis-Menten equation. Data obtained will be incorporated into a theoretical model to analyze transport and metabolic properties in IVD under mechanical strain. The outcome of these studies will provide insight into the etiological causes of disc degeneration and LBP and may also be used in the development of new strategies for treatment of LBP.

描述（由申请人提供）：腰痛（LBP）是美国的一个主要社会经济问题。虽然LBP的确切原因尚不清楚，但脊柱椎间盘（IVD）的退变被认为是主要原因。IVD是人体中最大的无血管结构，使水和溶质在椎间盘中的运输成为重要的营养机制。了解重要营养物质（如葡萄糖）的转运和代谢特性对于理解椎间盘退变的病理生理学非常重要。组织水平的机械力可以影响细胞水平的物理信号以及组织重塑通过组织材料性质的变化改变物理信号的方式，并且还可以调节可以控制椎间盘退变的开始和进展的细胞反应。因此，确定机械应变导致的组织特性变化对于理解IVD细胞对力和其他刺激的生物学反应是重要的，因此对于阐明椎间盘退变和LBP中涉及的病因学因素也是重要的。申请人的长期目标是：（1）更好地了解LBP发展中涉及的病理生理学;（2）进一步阐明正常和退行性IVD的转运和代谢特性;（3）开发评估和治疗椎间盘退行性变和LBP的新策略。本提案的主要目的是确定机械应变对非变性和变性人IVD组织中葡萄糖转运和代谢的影响。为了实现这一目标，拟议的计划分为三个研究相结合的理论和实验方法。在研究#1中，将使用1D非稳态扩散实验和定制设计的扩散池测定正常和变性人IVD组织中的应变依赖性葡萄糖扩散率（具体目标#1）。在研究#2中，将通过测量在压缩和自由膨胀条件下依次用组织样本平衡的三个浴槽内的葡萄糖浓度，测定正常和变性人IVD组织中葡萄糖的应变依赖性分配系数（特定目标#2）。在研究#3中，将通过监测水浴培养基中的葡萄糖浓度并使用FEM分析和Michaelis-Menten方程的理论曲线拟合来确定猪IVD细胞的菌株依赖性葡萄糖消耗率（具体目标#3）。将获得的数据纳入理论模型，以分析机械应变下IVD的运输和代谢特性。这些研究的结果将提供深入了解椎间盘退变和LBP的病因，也可能用于开发治疗LBP的新策略。