Our goal is to understand the cellular mechanisms that lead to arthritis, a painful and debilitating family of diseases that are the leading cause of disability in the developed countries. Even though little is known about the etiology of arthritis, it has been well established that the imbalance of a complex signaling network of regulatory proteins plays a major role in cartilage degeneration and the progression of the disease. Two different approaches will be combined to better understand the correlation between the protein signalling network and cartilage degeneration; a system biology approach and a biomechanical engineering approach.

The biomechanical engineering approach will be used to monitor the in-vitro degradation of cartilage explants by measuring their mechanical properties. Indentation tests will be combined with biphasic computational finite element models in order to measure the Young’s modulus and the permeability of the tissue.

The systems biology approach is based on a four-step feedback loop of manipulation-measurement-mining and modelling. Rather than focusing in a single pathway, the systems biology approach will allow us to investigate the possible crosstalks of several catabolic signalling cascades that govern cartilage degradation. The measurements of several intracellular and extracellular protein concentrations and their activity state will be analyzed using common signal proccessing algorithms in order to develop predictive models of the relationship between signalling network activities and phenotypic measurements of cartilage degradation.

CLINICAL IMPLICATIONS: The project tackles one of the most prevalent joint diseases in the developed countries that affect one out of every 6 people. The societal importance of understanding arthitis is enormous due to its economic, social and psychological costs that has been highlighted in the “European Action Towards Better Musculoskeletal Health”. The interdisciplinary and multidisciplinary nature of this project that combines areas of biomechanical engineering and system biology corresponds to a new approach for better understanding the molecular pathways of cartilage degradation and can lead us to new therapeutic interventions for arthritis. This project is funded by a European research grant (Marie Curie International Reintegration Grant).