Modelling osteomyelitis

BMC Bioinformatics

Research

Kathryn Atwell¹  Mohammad Ali Moni¹  Pietro Liò¹  Marco Viceconti²  Emanuela Merelli³  Nicola Paoletti³ 

[1] Computer Laboratory, Cambridge University, William Gates Building, 15 JJ Thomson Avenue, CB3 0FD, Cambridge, UK;Department of Mechanical Engineering, University of Sheffield, Sir Frederick Mappin Building, Mappin Street, S1 3JD, Sheffield, UK;School of Science and Technology, Computer Science Division, University of Camerino, Via Madonna delle Carceri 9, 62019, Camerino, MC, Italy;

关键词: Osteomyelitis;    osteoporosis;    bone remodelling;    RANKL;    RANK;    OPG;    NF-kB;    Staphylococcus aureus;   

DOI  :  10.1186/1471-2105-13-S14-S12

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Liò et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.