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

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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.