MOSPAIC · Modeling signaling pathways in cartilage degeneration
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2007-09-01 → 2009-08-31
- EU contribution
- €80,000
- Participants
- 1
- Scheme
- IRG
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Results in brief
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.
Data: CORDIS, © European Union
Project objective
Osteoarthritis (OA) and Rheumatoid Arthritis (RA) are painful and debilitating diseases characterized by cartilage degeneration, swelling, and decreased function of the synovial joints. It is the leading cause of disability in the developed countries affecting one of every six people and resulting in a significant cost on health and social care systems. Cartilage degeneration can be characterized by the imbalance of a complex network of regulatory proteins. Interleukin-1 (IL-1) and Tumour Necrosis Fact or-alpha (TNF-alpha) are two major cytokines responsible for the pathogenesis of arthritis. Current pharmaceutical interventions are based on the inhibition of these pro-inflammatory pathways. This project utilizes a multidisciplinary approach characterized by the fusion of two seemingly different areas: Biomechanics and Systems Biology. The biomechanical approach will be used to monitor the degradation of cartilage explants by measuring alterations on the mechanical properties. Indentation tests will be combined with biphasic finite element models in order to measure the Young's modulus and the permeability of the tissue.The systems biology approach will be employed to investigate the possible cross-talks of several signalling cascades that govern cartilage degeneration (i.e. TNF-alpha, IL-1, FasL). The measurements of several intracellular and extracellular protein concentrations as well as their activity state will be correlated to the alteration of the mechanical properties of the tissue by using a statistical approach such as principal component analysis and partial least squares regression. Predictive models between signalling network activities and phenotypic outcomes will be derived. The multidisciplinary approach of the project will shed light into the molecular pathways that govern cartilage degeneration. Intervention on these intracellular pathways with small molecule inhibitors can lead to new treatments of arthritis.
Original text from CORDIS.
Participants
- NATIONAL TECHNICAL UNIVERSITY OF ATHENS · ATHENSCoordinatorGreece
Links
Data: CORDIS, © European Union