Viscoelastic Properties of Normal and OA Chondrons

描述(申请人提供)：软骨细胞的机械环境是影响腹股沟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细胞、细胞周围基质和细胞外基质之间的相互作用。这项研究的目的是测量软骨细胞细胞周围基质的内在生物力学、物理化学和扩散特性，并验证这些特性在骨关节炎软骨中发生改变的假设。此外，我们认为在细胞周围基质中大量存在的VI型胶原影响该区域的物理性质。我们将使用几种新的实验技术结合理论建模来量化在分离的软骨模型和转基因小鼠中细胞周围基质的三相力学特性。本研究的具体目的是：1)利用微管吸入法和原子力显微镜测量正常软骨和骨关节炎软骨细胞周围基质的力学性质，并将这些发现纳入软骨细胞-基质相互作用的多相模型中，并使用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特性；3)确定删除VI型胶原对细胞周围基质的这些机械和物理化学特性的影响。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治疗骨关节炎的新的药物或生物物理干预措施。

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.