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中文摘要
翻译
软骨细胞的力学环境是影响健康和 关节的功能。软骨细胞暴露的机械信号取决于 细胞、细胞周围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性质, 软骨本研究的目的是测量固有的生物力学和扩散性能, 软骨细胞周基质,并测试假设,这些属性被改变, 骨关节炎软骨此外,我们提出,VI型胶原蛋白,这是丰富存在于 细胞周围基质影响该区域的物理性质。我们将使用几个新的 实验技术,以量化微机械行为的细胞周围基质使用分离的 _hondron模型。本研究的具体目的是:1)测量材料的力学性能, 应用微管抽吸和原子力技术从正常和骨关节炎软骨中提取软骨细胞基质 显微镜,将这些发现纳入软骨中细胞-基质相互作用的理论模型, 使用3D共聚焦显微镜验证这些预测; 2)测量 正常和OA软骨的细胞周基质; 3)确定正常或OA软骨的存在如何影响正常或OA软骨的生长。 细胞周基质影响软骨细胞对软骨细胞内动态压缩的代谢反应, 4)确定VI型胶原在人工基质的机械性能中起什么作用; 细胞周基质这项研究的长期目标是提高我们对 在正常和患病条件下调节软骨代谢的机械因素。更好的 对这些途径的了解将有望导致新药物的开发, 生物物理干预治疗骨关节炎。
英文摘要
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 _hondron model. The specific aims of this study are: 1) Measure the mechanical properties of the 3ericellular 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 lartificial 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.
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Synthetic Chronogenetic Gene Circuits for Circadian Cell Therapies
  • 批准号:
    10797183
  • 项目类别:
  • 资助金额:
    $37.63万
  • 财政年份:
    2023
  • 负责人:
    Farshid Guilak
  • 依托单位:
2023 Cartilage Biology and Pathology Gordon Research Conference and Gordon Research Seminar
  • 批准号:
    10605625
  • 项目类别:
  • 资助金额:
    $2.81万
  • 财政年份:
    2022
  • 负责人:
    Farshid Guilak
  • 依托单位:
Genome and epigenome editing of induced pluripotent stem cells for investigating osteoarthritis risk alleles
  • 批准号:
    10532032
  • 项目类别:
  • 资助金额:
    $20.75万
  • 财政年份:
    2022
  • 负责人:
    Farshid Guilak
  • 依托单位:
Deconstructing Cartilage Mechanotransduction by Piezo Channels
  • 批准号:
    10533155
  • 项目类别:
  • 资助金额:
    $1.86万
  • 财政年份:
    2022
  • 负责人:
    Farshid Guilak
  • 依托单位:
海外基金