Novel Determination Of Chondrocyte Material Properties

描述(由申请人提供)： 应对远离办公自动化：关于预防的科学会议 NIH对骨性关节炎的发病、进展和残疾的研究，这项建议 寻求提供有关软骨细胞特性的新信息，这些特性可以 用于更大努力地确定机械因素在骨关节炎中的作用 发展和进展(以及症状和残疾)。 骨关节炎(OA)是一种令人痛苦的衰弱疾病，发病时间为5分钟 占总人口的百分比和70%以上的美国人 65，并负责每年约286亿美元的相关 医疗费用。尽管人们对这些材料进行了广泛的研究 令人惊讶的是，软骨在生物力学载荷下的特性和行为 人们对软骨细胞的固有特性知之甚少，软骨细胞是指 包括软骨组织的活成分。的许多基本方面 细胞功能，包括形状、变形性、运动性、分裂、 ECM的生存能力和组织似乎受到 电池的机械性能。因此，只有牢牢把握 细胞和组织的材料行为都可以受到生物机械力的作用 和机械转导事件导致正常或 确定软骨的病理状态具有特异性和潜在的意义 确定因果关系。这款R21的具体目标 探索性赠款包括： 特定目标1.软骨细胞对外加载荷的力学响应 渗透负荷将被量化。渗透负荷使细胞研究成为可能 在不直接施加机械力的情况下的形状变化和变形 牢房。被动肿胀过程中软骨细胞反应的差异 (拉伸加载)和收缩(压缩加载)将被描述为 使用数字视频荧光和共聚焦显微镜以及原子 力显微镜(AFM)。 特指目标2.特指目标I的视频显微镜数据将合并 使用三相细胞模型(例如，固体、流体和离子相)来估计 软骨细胞的表观材料特性(例如，骨料模数和水力性能 渗透率)。这些性能将与压痕进行比较 从原子力显微镜数据的三相压痕分析中提取的性质 来自具体目标1。 如上所述的成功实施将使新的研究成为可能 关于生物力学影响在发育和发育中的作用的问题 办公自动化的进展有待解决。

DESCRIPTION (provided by applicant): In response to Stepping Away from OA: A Scientific Conference on the Prevention of Onset, Progression, and Disability of 0steoarthritis by NIH, this proposal seeks to provide new information regarding chondrocyte properties that can be used in the greater effort to determine the role of mechanical factors in OA development and progression (as well as in symptoms and disability). Osteoarthritis (OA) is a painfully debilitating disease, which strikes 5 percent of the general population and 70 percent of Americans over the age of 65 and is responsible for an estimated $28.6 billion per year in related medical costs. Although there has been extensive study of the material properties and behavior of cartilage under biomechanical loading, surprisingly little is known about the inherent properties of chondrocytes, the cells that comprise the living component of cartilage tissue. Many fundamental aspects of cellular function, including shape, deformability, motility, division, viability, and organization of the ECM, appear to be influenced by the mechanical properties of the cell. Therefore, only with a firm grasp of the material behavior of both cells and tissue can the role of biomechanical forces and mechanotransduction events that lead to the development of a normal or pathologic state in cartilage be determined with specificity and underlying cause and-effect relationships be identified. The specific aims of this R21 exploratory grant are: Specific Aim1. The chondrocyte mechanical response to applied loading via osmotic loading will be quantified. Osmotic loading permits the study of cell shape change and deformation without direct application of mechanical force to the cell. Differences in the chondrocyte response during passive swelling (tensile loading) and shrinking (compressive loading) will be characterized using digital video epifluorescence and confocal microscopy as well as atomic force microscopy (AFM). Specific Aim 2. The videomicroscopy data from Specific Aim I will be combined with a triphasic cell model (e.g., solid, fluid and ion phases) to estimate chondrocyte apparent material properties (e.g., aggregate modulus and hydraulic permeability). These properties will be compared with the indentation properties extracted from the triphasic indentation analyses of the AFM data from Specific Aim 1. Successful implementation of the aforementioned will permit new research questions regarding the role of biomechanical influences in the development and progression of OA to be addressed.