Computational modeling reveals a key role for polarized myeloid cells in controlling osteoclast activity during bone injury repair

Abstract Bone-forming osteoblasts and -resorbing osteoclasts control bone injury repair, and myeloid-derived cells such as monocytes and macrophages are known to influence their behavior. However, precisely how these multiple cell types coordinate and regulate each other over time within the bone ma...

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Autores principales:	Chen Hao Lo, Etienne Baratchart, David Basanta, Conor C. Lynch
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/94c5c6de4a724913a208a6936436ef58
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spelling	oai:doaj.org-article:94c5c6de4a724913a208a6936436ef582021-12-02T17:05:49ZComputational modeling reveals a key role for polarized myeloid cells in controlling osteoclast activity during bone injury repair10.1038/s41598-021-84888-12045-2322https://doaj.org/article/94c5c6de4a724913a208a6936436ef582021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84888-1https://doaj.org/toc/2045-2322Abstract Bone-forming osteoblasts and -resorbing osteoclasts control bone injury repair, and myeloid-derived cells such as monocytes and macrophages are known to influence their behavior. However, precisely how these multiple cell types coordinate and regulate each other over time within the bone marrow to restore bone is difficult to dissect using biological approaches. Conversely, mathematical modeling lends itself well to this challenge. Therefore, we generated an ordinary differential equation (ODE) model powered by experimental data (osteoblast, osteoclast, bone volume, pro- and anti-inflammatory myeloid cells) obtained from intra-tibially injured mice. Initial ODE results using only osteoblast/osteoclast populations demonstrated that bone homeostasis could not be recovered after injury, but this issue was resolved upon integration of pro- and anti-inflammatory myeloid population dynamics. Surprisingly, the ODE revealed temporal disconnects between the peak of total bone mineralization/resorption, and osteoblast/osteoclast numbers. Specifically, the model indicated that osteoclast activity must vary greatly (> 17-fold) to return the bone volume to baseline after injury and suggest that osteoblast/osteoclast number alone is insufficient to predict bone the trajectory of bone repair. Importantly, the values of osteoclast activity fall within those published previously. These data underscore the value of mathematical modeling approaches to understand and reveal new insights into complex biological processes.Chen Hao LoEtienne BaratchartDavid BasantaConor C. LynchNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chen Hao Lo Etienne Baratchart David Basanta Conor C. Lynch Computational modeling reveals a key role for polarized myeloid cells in controlling osteoclast activity during bone injury repair
description	Abstract Bone-forming osteoblasts and -resorbing osteoclasts control bone injury repair, and myeloid-derived cells such as monocytes and macrophages are known to influence their behavior. However, precisely how these multiple cell types coordinate and regulate each other over time within the bone marrow to restore bone is difficult to dissect using biological approaches. Conversely, mathematical modeling lends itself well to this challenge. Therefore, we generated an ordinary differential equation (ODE) model powered by experimental data (osteoblast, osteoclast, bone volume, pro- and anti-inflammatory myeloid cells) obtained from intra-tibially injured mice. Initial ODE results using only osteoblast/osteoclast populations demonstrated that bone homeostasis could not be recovered after injury, but this issue was resolved upon integration of pro- and anti-inflammatory myeloid population dynamics. Surprisingly, the ODE revealed temporal disconnects between the peak of total bone mineralization/resorption, and osteoblast/osteoclast numbers. Specifically, the model indicated that osteoclast activity must vary greatly (> 17-fold) to return the bone volume to baseline after injury and suggest that osteoblast/osteoclast number alone is insufficient to predict bone the trajectory of bone repair. Importantly, the values of osteoclast activity fall within those published previously. These data underscore the value of mathematical modeling approaches to understand and reveal new insights into complex biological processes.
format	article
author	Chen Hao Lo Etienne Baratchart David Basanta Conor C. Lynch
author_facet	Chen Hao Lo Etienne Baratchart David Basanta Conor C. Lynch
author_sort	Chen Hao Lo
title	Computational modeling reveals a key role for polarized myeloid cells in controlling osteoclast activity during bone injury repair
title_short	Computational modeling reveals a key role for polarized myeloid cells in controlling osteoclast activity during bone injury repair
title_full	Computational modeling reveals a key role for polarized myeloid cells in controlling osteoclast activity during bone injury repair
title_fullStr	Computational modeling reveals a key role for polarized myeloid cells in controlling osteoclast activity during bone injury repair
title_full_unstemmed	Computational modeling reveals a key role for polarized myeloid cells in controlling osteoclast activity during bone injury repair
title_sort	computational modeling reveals a key role for polarized myeloid cells in controlling osteoclast activity during bone injury repair
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/94c5c6de4a724913a208a6936436ef58
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Computational modeling reveals a key role for polarized myeloid cells in controlling osteoclast activity during bone injury repair

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