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Issue No.05 - Sept.-Oct. (2012 vol.9)
pp: 1366-1378
Nicola Paoletti , Sch. of Sci. & Technol., Univ. of Camerino, Camerino, Italy
Pietro Lio , Comput. Lab., Univ. of Cambridge, Cambridge, UK
Emanuela Merelli , Sch. of Sci. & Technol., Univ. of Camerino, Camerino, Italy
Marco Viceconti , Dept. of Mech. Eng., Univ. of Sheffield, Sheffield, UK
ABSTRACT
Our work focuses on bone remodeling with a multiscale breadth that ranges from modeling intracellular and intercellular RANK/RANKL signaling to tissue dynamics, by developing a multilevel modeling framework. Several important findings provide clear evidences of the multiscale properties of bone formation and of the links between RANK/RANKL and bone density in healthy and disease conditions. Recent studies indicate that the circulating levels of OPG and RANKL are inversely related to bone turnover and Bone Mineral Density (BMD) and contribute to the development of osteoporosis in postmenopausal women, and thalassemic patients. We make use of a spatial process algebra, the Shape Calculus, to control stochastic cell agents that are continuously remodeling the bone. We found that our description is effective for such a multiscale, multilevel process and that RANKL signaling small dynamic concentration defects are greatly amplified by the continuous alternation of absorption and formation resulting in large structural bone defects. This work contributes to the computational modeling of complex systems with a multilevel approach connecting formal languages and agent-based simulation tools.
INDEX TERMS
tissue engineering, bone, calculus, cellular biophysics, diseases, formal languages, medical computing, process algebra, stochastic systems, formal languages, multilevel computational modeling, quantitative analysis, bone remodeling, multiscale breadth, intracellular RANK-RANKL signaling, intercellular RANK-RANKL signaling, tissue dynamics, disease, bone mineral density, osteoporosis, postmenopausal women, thalassemic patients, spatial process algebra, Shape Calculus, stochastic cell agents, dynamic concentration defects, structural bone defects, agent-based simulation tools, Bones, Shape, Three dimensional displays, Calculus, Computational modeling, Biological system modeling, Osteoporosis, agent-based simulation., Osteoporosis, multilevel, shape calculus, bone remodeling, multiscale, RANK/RANKL
CITATION
Nicola Paoletti, Pietro Lio, Emanuela Merelli, Marco Viceconti, "Multilevel Computational Modeling and Quantitative Analysis of Bone Remodeling", IEEE/ACM Transactions on Computational Biology and Bioinformatics, vol.9, no. 5, pp. 1366-1378, Sept.-Oct. 2012, doi:10.1109/TCBB.2012.51
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