Kaul, H., Hall, B.K., Newby, C. et al. (1 more author) (2015) Synergistic activity of polarised osteoblasts inside condensations cause their differentiation. Scientific Reports, 5. 11838 . ISSN 2045-2322
Abstract
Condensation of pre-osteogenic, or pre-chondrogenic, cells is the first of a series of processes that initiate skeletal development. We present a validated, novel, three-dimensional agent-based model of in vitro intramembranous osteogenic condensation. The model, informed by system heterogeneity and relying on an interaction-reliant strategy, is shown to be sensitive to 'rules' capturing condensation growth and can be employed to track activity of individual cells to observe their macroscopic impact. It, therefore, makes available previously inaccessible data, offering new insights and providing a new context for exploring the emergence, as well as normal and abnormal development, of osteogenic structures. Of the several stages of condensation we investigate osteoblast 'burial' within the osteoid they deposit. The mechanisms underlying entrapment - required for osteoblasts to differentiate into osteocytes - remain a matter of conjecture with several hypotheses claiming to capture this important transition. Computational examination of this transition indicates that osteoblasts neither turn off nor slow down their matrix secreting genes - a widely held view; nor do they secrete matrix randomly. The model further reveals that osteoblasts display polarised behaviour to deposit osteoid. This is both an important addition to our understanding of condensation and an important validation of the model's utility.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015. Himanshu Kaul, Brian K. Hall, Chris Newby and Yiannis Ventikos . This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Computational models Bone development Stem-cell differentiation |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Computer Science (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 17 Jul 2015 10:11 |
Last Modified: | 17 Jul 2015 10:11 |
Published Version: | http://dx.doi.org/10.1038/srep11838 |
Status: | Published |
Publisher: | Nature Publishing Group |
Refereed: | Yes |
Identification Number: | 10.1038/srep11838 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:87943 |