Chondrocyte mechanotransduction and the purinergic receptor pathway

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The overall goal of the proposed research program is to investigate the purinergic pathway in the response of cartilage cells to mechanical loading. The application of mechanical loading to tissue engineered cartilage constructs is a widely used method to accelerate tissue growth and enhance tissue mechanical properties. However, there are two major drawbacks with the use of mechanical stimuli to elicit such effects: (i) the available window to apply loading is limited as the cells rapidly desensitize to the stimulus, and (ii) the application of mechanical stimuli to tissue constructs requires the use of complex equipment and a high degree of operator training. Recently, it has been identified that cartilage cells utilize adenosine triphosphate (ATP) as a signalling molecule in the mechanotransduction process. Mechanical loading elicits the release of ATP which stimulate other cells to synthesize tissue. This pathway (purinergic receptor pathway) is tightly regulated as these cells also express enzymes which degrade ATP, thereby desensitizing the cells to the imposed mechanical stimulus. The proposed research program to investigate the involvement of the purinergic receptor pathway during chondrocyte mechanotransduction will be carried out in two projects: (i) purinergic receptor pathway involvement in cellular desensitization to mechanical load, and (i) directly harnessing the purinergic receptor pathway through exogenous ATP. This research will further our knowledge of mechanotransduction processes which have direct applications to disease states (e.g. osteoarthritis) that are characterized by an impaired response to mechanical loading. In addition, this research will facilitate the development of functional engineered tissues to help create of new treatment options for patients suffering from severe arthritic disorders. Over the next five years, this research program will prepare 7 HQPs (2 PhD; 5 undergraduate) for professional careers in biomedical engineering. HQPs working on these projects will have the opportunity to be involved in inter-disciplinary research and to acquire fundamental knowledge and practical experience in the area of tissue engineering and regenerative medicine.