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BMC Bioinformatics

, 13:S12

First Online: 07 September 2012

Abstract

BackgroundThis work focuses on the computational modelling of osteomyelitis, a bone pathology caused by bacteria infection mostly Staphylococcus aureus. The infection alters the RANK-RANKL-OPG signalling dynamics that regulates osteoblasts and osteoclasts behaviour in bone remodelling, i.e. the resorption and mineralization activity. The infection rapidly leads to severe bone loss, necrosis of the affected portion, and it may even spread to other parts of the body. On the other hand, osteoporosis is not a bacterial infection but similarly is a defective bone pathology arising due to imbalances in the RANK-RANKL-OPG molecular pathway, and due to the progressive weakening of bone structure.

ResultsSince both osteoporosis and osteomyelitis cause loss of bone mass, we focused on comparing the dynamics of these diseases by means of computational models. Firstly, we performed meta-analysis on a gene expression data of normal, osteoporotic and osteomyelitis bone conditions. We mainly focused on RANKL-OPG signalling, the TNF and TNF receptor superfamilies and the NF-k B pathway. Using information from the gene expression data we estimated parameters for a novel model of osteoporosis and of osteomyelitis. Our models could be seen as a hybrid ODE and probabilistic verification modelling framework which aims at investigating the dynamics of the effects of the infection in bone remodelling. Finally we discuss different diagnostic estimators defined by formal verification techniques, in order to assess different bone pathologies osteopenia, osteoporosis and osteomyelitis in an effective way.

ConclusionsWe present a modeling framework able to reproduce aspects of the different bone remodeling defective dynamics of osteomyelitis and osteoporosis. We report that the verification-based estimators are meaningful in the light of a feed forward between computational medicine and clinical bioinformatics.

KeywordsOsteomyelitis osteoporosis bone remodelling RANKL RANK OPG NF-kB Staphylococcus aureus.  Download fulltext PDF



Author: Pietro Liò - Nicola Paoletti - Mohammad Ali Moni - Kathryn Atwell - Emanuela Merelli - Marco Viceconti

Source: https://link.springer.com/







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