2016 Conference on Computational Modelling with COPASI
Manchester Institute of Biotechnology, 12th – 13th May, 2016
1 - Newcastle University, UK, 2 - University of Liverpool, UK
Keywords: TGF-β, Osteoarthritis, systems biology, inflammation
Osteoarthritis (OA) is a degenerative condition that is caused by the dysregulation of many molecular signalling pathways. TGF-β is a cytokine with pluripotent effects on OA development, initially protecting against inflammation driven damage, whilst promoting the restoration of cartilage. However, as we age TGF-β promotes induction of catabolic enzymes causing excessive damage to cartilage. A change in the ratio of two TGF-β type one receptors has been shown, the shift correlating with the spontaneous development of OA in mice models. Dr Carole Proctor created a model in copasi to show the stochastic changes in TGF-β signalling during ageing. We aim to expand this model incorporating how these changes affect the cells response to an inflammatory stimulus. Using a chondrocyte specific cell line (SW1353) in combination with this modelling based approach we aim to identify the key changes in the pathway that turn TGF-β from a protective to destructive cytokine.