Final Activity Report Summary - MOSPAIC (Modeling Signaling Pathways In Cartilage Degeneration) The objective of the project was to employ a systems biology approach and a bioengineering approach in order to model the signalling pathways involved in cartilage degeneration. For the first part of the study (Systems Biology approach) we were able to identify the effects of drugs on the signalling pathways of cells by combining novel experimental and computational techniques. In the second part of the project (bioengineering approach) we were able to quantify cartilage degeneration by measuring the mechanical properties of the tissue (i.e. decreased stiffness and increased permeability shows cartilage degradation). The project has led to one published paper in top-tier journal, two follow-up papers in top-tier journals, one book chapter, one submitted paper, two papers in preparation and nine conferences (seven presentations and two posters). The project uncovered molecular pathways that govern cartilage degeneration and the development of osteoarthritis, a painful disease that is the leading cause of disability in the developed countries, affects one of every six people, and results in a significant cost on health and social care systems. Intervention on these intracellular pathways with small molecule inhibitors can lead to new treatments of arthritis. This research is continued successfully from the same investigator via 4 follow ups grants that has been granted and two that has been submitted. In a more general aspect, the MC grant gave the opportunity for Leonidas Alexopoulos to establish himself in Europe, built his systems biology and bioengineering group at the National Technical University of Athens, create new undergraduate and graduate courses in the curriculum of his host department in bioengineering and systems biology field and receive four follow up grants from European institutions and companies.