Integrative mathematical modelling of physiological- and molecular factors of osteoarthritis of the knee

M. v. Kleist (DFG-NWGL), C. Schütte, Inst. of Mathematics and
Computer Science, Freie Universität of Berlin

Abstract: Osteoarthritis of the knee (OAK) is a complex multi-factorial condition that is characterised by a lack of hyaline cartilage self repair 1, inflammation & pain 2. As for many other multi-factorial conditions, computational models may be useful tools of direct clinical relevance that allow studying the interaction of putative factors. Within this subproject, we want to develop a comprehensive computational model of cartilage homeostasis that will help us to understand and to evaluate the onset and progression of OAK. While the underlying mechanisms of OAK remain unknown, several factors have been previously associated with osteoarthritis  and studied in isolation, such as cell density-dependent extracellular matrix (EM) generation 3,4, EM metabolism 5, the effect of nutrient gradients 5,6 and the influence of (mechano-) growth factors 7.

Our research group has a broad expertise in interdisciplinary research in biomedicine 8,11 with a particular focus on mechanistic mathematical modelling 8,9 including in vitro to in vivo extrapolation, as well as the analysis of complex clinical samples 10. Within this consortium, we aspire to combine biochemical data from PrevOP subprojects SP1-3 (inflammation, cartilage self-repair & pain) and OVERLOAD projects SP5, 7-8 (fluid transport, mechano-sensitive signalling, cartilage self-repair), to successively develop mathematical models of cartilage homeostasis. Particularly, integration of results from OVERLOAD SP5 may allow to couple image-derived clinical data to metabolic events in the cartilage. The developed comprehensive model of OAK will further our understanding of the  disease and the interplay of the mentioned factors, provide insights into disease mechanisms and strategies for its prevention (like, e.g. physical training). The aim of the project is thus to provide a translational framework between in vitro bio-molecular studies, ex vivo analysis, animal models and human patients with OAK (clinical projects in PrevOP/OVERLOAD).


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