VISCOELASTIC PROPERTIES OF NORMAL AND OA CHONDRONS

正常软骨和 OA 软骨的粘弹性特性

• 批准号: 6574102
• 负责人: Farshid Guilak
• 金额: $ 34.65万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6574102
• 关键词: articular cartilage; atomic force microscopy; biomechanics; cell cell interaction; chondrocytes; collagen; confocal scanning microscopy; diffusion; digital imaging; extracellular matrix; human tissue; laboratory mouse; osteoarthritis; physical property; viscosity

DESCRIPTION (provided by applicant): The mechanical environment of the chondrocytes is an important factor that affects the health and function of the diarthrodial joint. The mechanical signals to which chondrocytes are exposed depend on the biomechanical interactions between the cell, pericellular matrix, and extracellular matrix. Currently, there is little or no information available on the mechanical properties of the pericellular matrix of articular cartilage. The goals of this study are to measure the intrinsic biomechanical and diffusion properties of the chondrocyte pericellular matrix, and to test the hypothesis that these properties are altered in osteoarthritic cartilage. Furthermore, we propose that type VI collagen, which is abundantly present in the pericellular matrix, influences the physical properties of this region. We will use several novel experimental techniques to quantify the micromechanical behavior of pericellular matrix using the isolated chondron model. The Specific Aims of this study are: (1) measure the mechanical properties of the pericellular matrix from normal and osteoarthritic cartilage using micropipette aspiration and atomic force microscopy, incorporate these findings in a theoretical model of cell-matrix interactions in cartilage, and validate these predictions using 3D confocal microscopy; (2) measure the diffusion properties of the pericellular matrix of normal and OA cartilage; (3) determine how the presence of a normal or OA pericellular matrix influences the metabolic response of chondrocytes to dynamic compression within an artificial matrix; and (4) determine what role type VI collagen plays in the mechanical properties of the pericellular matrix. The long-term goals of this study are to improve our understanding of the role of mechanical factors in the regulation of cartilage metabolism in normal and diseased conditions. A better understanding of these pathways will hopefully lead to the development of new pharmaceutical or biophysical interventions for the treatment of osteoarthritis.

描述（由申请人提供）：软骨细胞的力学环境是影响关节健康和功能的重要因素。软骨细胞所暴露的机械信号取决于细胞、细胞周基质和细胞外基质之间的生物力学相互作用。目前，有很少或没有关于关节软骨细胞周围基质的机械性能的信息。本研究的目的是测量软骨细胞周基质的内在生物力学和扩散特性，并检验这些特性在骨关节炎软骨中改变的假设。此外，我们提出，VI型胶原，这是大量存在于细胞周围基质，影响该地区的物理性质。我们将使用几种新的实验技术，以量化的孤立软骨模型的细胞周围基质的微观力学行为。本研究的具体目的是：（1）使用微管抽吸和原子力显微镜测量正常和骨关节炎软骨细胞周围基质的力学性质，将这些发现纳入软骨细胞-基质相互作用的理论模型中，并使用3D共聚焦显微镜验证这些预测;（2）测量正常和骨关节炎软骨细胞周围基质的扩散性质;（3）确定正常或OA细胞周基质的存在如何影响软骨细胞对人工基质内动态压缩的代谢反应;和（4）确定VI型胶原在细胞周基质的机械性质中起什么作用。这项研究的长期目标是提高我们对机械因素在正常和疾病条件下调节软骨代谢中的作用的理解。更好地了解这些途径将有望导致新的药物或生物物理干预治疗骨关节炎的发展。