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实验技术与理论建模相结合，以量化分离的软骨模型和转基因小鼠中的细胞周基质的三相机械性能。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多相模型，并使用共聚焦显微镜验证这些预测; 2）测量正常和OA软骨细胞周围基质的扩散性质; 3）确定去除VI型胶原对细胞周围基质的这些机械和物理化学性质的影响。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 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 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 multiphasic model of cell-matrix interactions in cartilage, and validate these predictions using confocal microscopy; 2) Measure the diffusion properties of the pericellular matrix of normal and OA cartilage; 3) Determine the effect of deleting type VI collagen on these mechanical and physicochemical 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.