Viscoelastic Properties of Normal and OA Chondrons

正常软骨和 OA 软骨的粘弹性

基本信息

批准号：
8658344
负责人：
Farshid Guilak
金额：
$ 32.19万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-01-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8658344
关键词：
Abbreviations Adult Affect Animals Atomic Force Microscopy Biochemical Biomechanics Boundary Elements Cartilage Cell model Cells Characteristics Chondrocytes Collagen Collagen Type VI Complex Confocal Microscopy Coupled Degenerative polyarthritis Development Diffusion Disease Elements Environment Equilibrium Exhibits Experimental Models Extracellular Matrix Finite Element Analysis Fluorescence Geometry Goals Health Histology In Situ Intervention Ions Joints Knock-out Lead Liquid substance Maps Measurement Measures Mechanics Mediating Methods Microscopy Modeling Mus Osmolalities Osteoarthrosis Deformans Pathway interactions Permeability Pharmacologic Substance Photobleaching Play Property Regulation Residual state Role Scanning Signal Transduction Site Solid Staging Stress Structure Swelling Techniques Testing Theoretical model Three-Dimensional Imaging Tissues Transgenic Mice Transport Process Wild Type Mouse articular cartilage base cartilage metabolism diffusion anisotropy fluorescence imaging improved macromolecule novel physical property research study response

项目摘要

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 biomechanical and physicochemical signals to which chondrocytes are exposed depend on the interactions between the cell, pericellular matrix, and extracellular matrix of articular cartilage. The goals of this study are to measure the intrinsic biomechanical, physicochemical, 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 micromechanical experimental techniques in combination with theoretical modeling to quantify the triphasic mechanical properties of the pericellular matrix in the isolated chondron model and in transgenic mice. The aims of this project are to measure the triphasic mechanical properties of the pericellular matrix from normal and osteoarthritic cartilage using atomic force microscopy, incorporate these findings in a theoretical triphasic model of cell-matrix interactions in cartilage, and validate these predictions using confocal microscopy. We will also use new fluorescence-based methods to measure the diffusion properties of the pericellular matrix of normal and OA cartilage. Finally, we will determine the role of type VI collagen on the triphasic mechanical properties of the pericellular matrix and subsequently, the mechanical environment of the chondrocyte. 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（申请人提供）：软骨细胞的机械环境是影响关节健康和功能的重要因素。软骨细胞所暴露的生物力学和物理化学信号取决于关节软骨的细胞、细胞周基质和细胞外基质之间的相互作用。本研究的目的是测量软骨细胞周基质的内在生物力学、物理化学和扩散特性，并检验这些特性在骨关节炎软骨中发生改变的假设。此外，我们认为，大量存在于细胞周基质中的 VI 型胶原蛋白会影响该区域的物理特性。我们将使用几种新颖的微机械实验技术与理论模型相结合来量化分离软骨模型和转基因小鼠中细胞周基质的三相机械特性。该项目的目的是使用原子力显微镜测量正常和骨关节炎软骨的细胞周基质的三相机械特性，将这些发现纳入软骨中细胞-基质相互作用的理论三相模型中，并使用共聚焦显微镜验证这些预测。我们还将使用新的基于荧光的方法来测量正常软骨和骨关节炎软骨的细胞周基质的扩散特性。最后，我们将确定 VI 型胶原蛋白对细胞周基质的三相机械特性以及随后的软骨细胞的机械环境的作用。这项研究的长期目标是提高我们对机械因素在正常和患病条件下软骨代谢调节中的作用的理解。对这些途径的更好理解将有望导致开发新的药物或生物物理干预措施来治疗骨关节炎。