The Role of Genetic Modifications, Age and Exercise on Cartilage Biomechanics using Genetically Engineered Mice

使用基因工程小鼠研究基因修饰、年龄和运动对软骨生物力学的作用

• 批准号: 1536233
• 负责人: Christine Ortiz
• 金额: $ 39.85万
• 依托单位: Massachusetts Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1536233&HistoricalAwards=false
• 关键词: Role; Genetic; Modifications; Age; Exercise

Cartilage is a thin tissue covering the ends of bones which provides a low-friction interface for the easy motion of articular joints such as the knee, shoulder, hip and others. The biomechanical properties and low friction of cartilage often make it possible for this thin tissue to carry high load with up to millions of cycles per year for a full lifetime. The genetic sources of cartilage properties are not well understood. This research will use novel technology to measure biomechanical properties of cartilage from mice that were genetically modified to determine what genes contribute to cartilage mechanical properties across the age of the animals. These assessments of cartilage function and aging will provide important basic understanding of how genes interact with activity and time to produce function. The results and new mechanical testing method will also have application to the detection of the early stages of arthritis. The application to arthritis could have a societal impact because it is a leading cause of disability for hundreds of millions of people worldwide. The biomechanical methods developed in this study will also work for measuring properties of other materials including artificial hydrogels and engineered tissues as well as natural animal tissues such as: tectorial membrane, ligament, meniscus and skin. This multidisciplinary research program will enable for the first time a comprehensive and quantitative study of biological factors by measuring nano- scale solid-fluid interactions within murine cartilage tissue and key matrix molecules (i.e., aggrecan and collagen type II) over a frequency range pertinent to walking, running and impact-injury using atomic force microscopy. The knee joints from well-established mouse models will be provided from animals allowed normal ambulation and those exercised on running wheels, at three selected age groups. The research will determine the nanodynamic biomechanical measurements of cartilage tissue as well as of isolated aggrecan brush layers using an aggrecan decorated probe tip. These tissue and molecular assessments will be tested for their dependence on genetic, excercise and age factors to determine how the modified mice differ from normal.

腕骨是覆盖骨末端的薄组织，其提供低摩擦界面以便于关节（例如膝、肩、髋等）的运动。 软骨的生物力学特性和低摩擦力通常使这种薄组织能够在整个生命周期内每年承受高达数百万次的高负荷。 软骨特性的遗传来源还不清楚。 这项研究将使用新技术来测量转基因小鼠软骨的生物力学特性，以确定哪些基因对动物年龄段的软骨力学特性有贡献。 这些软骨功能和老化的评估将提供重要的基本了解基因如何与活动和时间相互作用，以产生功能。 结果和新的机械测试方法也将应用于关节炎早期阶段的检测。关节炎的应用可能会产生社会影响，因为它是全球数亿人残疾的主要原因。 本研究中开发的生物力学方法也将用于测量其他材料的性能，包括人工水凝胶和工程组织以及天然动物组织，如：覆膜，韧带，半月板和皮肤。这项多学科研究计划将首次通过测量小鼠软骨组织和关键基质分子（即，聚集蛋白聚糖和II型胶原蛋白）在与行走、跑步和撞击损伤相关的频率范围内使用原子力显微镜进行。将从三个选定年龄组的允许正常截肢和在跑步轮上运动的动物中提供良好建立的小鼠模型的膝关节。这项研究将确定软骨组织的纳米动力学生物力学测量，以及使用aggrecan装饰探针尖端的孤立aggrecan刷层。这些组织和分子评估将测试它们对遗传、运动和年龄因素的依赖性，以确定修饰小鼠与正常小鼠的差异。