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泻关节健康和功能的重要因素。软骨细胞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，关于关节软骨细胞周围基质的力学特性的研究很少或没有。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，我们认为大量存在于细胞周围基质中的VI型胶原会影响该区域的物理性质。我们将使用几种新的实验技术来量化使用分离的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)使用微移液管吸吸和原子力显微镜测量正常软骨和骨关节炎软骨的细胞周围基质的力学特性，将这些发现纳入软骨细胞-基质相互作用的理论模型，并使用3D共聚焦显微镜验证这些预测；(2)测定正常软骨和OA软骨细胞周基质的扩散特性；(3)确定正常或OA细胞周围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；(4)确定VI型胶原在细胞周围基质的力学性能中所起的作用。本研究的长期目标是提高我们对机械因素在正常和病变情况下软骨代谢调节中的作用的理解。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 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.