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

软骨是覆盖在骨骼末端的一种薄组织，它为膝关节、肩膀、髋关节和其他关节的轻松运动提供了一个低摩擦的界面。软骨的生物力学特性和低摩擦力通常使这种薄组织在一生中能够承载高负荷，每年高达数百万次。软骨特性的遗传来源还不是很清楚。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性能，以确定哪些基因对动物年龄的软骨机械性能有影响。这些对软骨功能和衰老的评估将为基因如何与活动和时间相互作用产生功能提供重要的基本理解。这一结果和新的机械测试方法也将应用于关节炎的早期检测。应用于关节炎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。这项研究中开发的生物力学方法也将适用于测量其他材料的性能，包括人造水凝胶和工程组织以及天然动物组织，如覆盖膜、韧带、半月板和皮肤。这一多学科研究计划将首次实现对生物因素的全面和定量研究，方法是使用原子力显微镜在与步行、跑步和撞击损伤相关的频率范围内测量小鼠软骨组织和关键基质分子(即聚集素和II型胶原)内的纳米级固-液相互作用。来自成熟的小鼠模型的膝关节将来自允许正常行走的动物和那些在跑步轮子上锻炼的动物，在三个选定的年龄段。这项研究将确定软骨组织的纳米动态生物力学测量，以及使用装饰了aggrecan的探头尖端对孤立的aggrecan刷子层的测量。这些组织和分子评估将测试它们对遗传、锻炼和年龄因素的依赖性，以确定修改后的小鼠与正常小鼠有何不同。

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.