Viscoelastic Properties of Normal and OA Chondrons

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，并检验骨关节炎软骨中这些特性发生改变的假设。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微机械实验技术结合理论建模，以量化的三相机械性能的细胞周围基质中的分离软骨模型和转基因小鼠。本项目的目的是测量的三相机械性能的细胞周围基质从正常和骨关节炎软骨使用原子力显微镜，将这些发现在软骨中的细胞-基质相互作用的理论三相模型，并验证这些预测使用共聚焦显微镜。我们还将使用新的荧光为基础的方法来测量正常和OA软骨的细胞周围基质的扩散特性。最后，我们将确定VI型胶原蛋白对细胞周围基质的三相机械性能的作用，并随后确定软骨细胞的机械环境。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。

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.