Objective Articular cartilage serves as a load bearing material for synovial joints, transmitting loads while maintaining low friction and wear. Progressive degeneration of the tissue leads to osteoarthritis (OA), a debilitating condition characterized by pain and severe limitations in mobility. OA is highly prevalent amongst the EU population and is associated with significant economic burdens. An improved understanding of the underlying mechanisms that defeat normal tissue maintenance and lead to joint degeneration is critical for the development of successful treatment strategies. This project examines a newly hypothesized intrinsic repair mechanism in articular cartilage, mediated by the extracellular activation of large stores of latent (inactive) TGF-beta through the action of chondrocyte-secreted proteases. This proposal hypothesizes that this mechanism maintains cartilage homeostasis in response to a wide range of physiologic mechanical loading conditions, but is unable to maintain tissue subjected to excessive loading, as seen in OA associated risk factors (e.g. joint instability, high impact activities). This hypothesized mechanism will be investigated through the implementation of an in vitro experimental model system, consisting of the mechanical loading of articular cartilage explants and the sophisticated biochemical analysis of resulting TGF-beta activation and microstructural alterations to the cartilage ECM. This state-of-the-art proposal represents an exciting, unique opportunity to bring together the complementary skillsets of the candidate and the Stevens Group, with their respective expertise in biomechanics and biochemistry, to uncover fundamental mechanisms in cartilage mechanobiology. This mutually beneficial cooperation between Europe and the U.S. can promote the development of successful treatments for OA, including tissue engineering and molecular intervention strategies that will impact the EU community at large. Fields of science natural sciencesbiological sciencesbiochemistrymedical and health sciencesmedical biotechnologytissue engineeringnatural sciencesbiological sciencesbiophysicsmedical and health sciencesbasic medicinephysiologyhomeostasis Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2013-IIF - Marie Curie Action: "International Incoming Fellowships" Call for proposal FP7-PEOPLE-2013-IIF See other projects for this call Funding Scheme MC-IIF - International Incoming Fellowships (IIF) Coordinator IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE EU contribution € 221 606,40 Address SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON United Kingdom See on map Region London Inner London — West Westminster Activity type Higher or Secondary Education Establishments Administrative Contact Shaun Power (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
