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Trabecular bone remodeling in the aging mouse: A micro-multiphysics agent-based in silico model using single-cell mechanomics
Bone remodeling is regulated by the interaction between different cells and tissues across many spatial and temporal scales. Notably, in silico models are regarded as powerful tools to further understand the signaling pathways that regulate this intricate spatial cellular interplay. To this end, we...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017748/ https://www.ncbi.nlm.nih.gov/pubmed/36937760 http://dx.doi.org/10.3389/fbioe.2023.1091294 |
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author | Boaretti, Daniele Marques, Francisco C. Ledoux, Charles Singh, Amit Kendall, Jack J. Wehrle, Esther Kuhn, Gisela A. Bansod, Yogesh D. Schulte, Friederike A. Müller, Ralph |
author_facet | Boaretti, Daniele Marques, Francisco C. Ledoux, Charles Singh, Amit Kendall, Jack J. Wehrle, Esther Kuhn, Gisela A. Bansod, Yogesh D. Schulte, Friederike A. Müller, Ralph |
author_sort | Boaretti, Daniele |
collection | PubMed |
description | Bone remodeling is regulated by the interaction between different cells and tissues across many spatial and temporal scales. Notably, in silico models are regarded as powerful tools to further understand the signaling pathways that regulate this intricate spatial cellular interplay. To this end, we have established a 3D multiscale micro-multiphysics agent-based (micro-MPA) in silico model of trabecular bone remodeling using longitudinal in vivo data from the sixth caudal vertebra (CV6) of PolgA((D257A/D257A)) mice, a mouse model of premature aging. Our in silico model includes a variety of cells as single agents and receptor-ligand kinetics, mechanomics, diffusion and decay of cytokines which regulate the cells’ behavior. We highlighted its capabilities by simulating trabecular bone remodeling in the CV6 of five mice over 4 weeks and we evaluated the static and dynamic morphometry of the trabecular bone microarchitecture. Based on the progression of the average trabecular bone volume fraction (BV/TV), we identified a configuration of the model parameters to simulate homeostatic trabecular bone remodeling, here named basal. Crucially, we also produced anabolic, anti-anabolic, catabolic and anti-catabolic responses with an increase or decrease by one standard deviation in the levels of osteoprotegerin (OPG), receptor activator of nuclear factor kB ligand (RANKL), and sclerostin (Scl) produced by the osteocytes. Our results showed that changes in the levels of OPG and RANKL were positively and negatively correlated with the BV/TV values after 4 weeks in comparison to basal levels, respectively. Conversely, changes in Scl levels produced small fluctuations in BV/TV in comparison to the basal state. From these results, Scl was deemed to be the main driver of equilibrium while RANKL and OPG were shown to be involved in changes in bone volume fraction with potential relevance for age-related bone features. Ultimately, this micro-MPA model provides valuable insights into how cells respond to their local mechanical environment and can help to identify critical pathways affected by degenerative conditions and ageing. |
format | Online Article Text |
id | pubmed-10017748 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100177482023-03-17 Trabecular bone remodeling in the aging mouse: A micro-multiphysics agent-based in silico model using single-cell mechanomics Boaretti, Daniele Marques, Francisco C. Ledoux, Charles Singh, Amit Kendall, Jack J. Wehrle, Esther Kuhn, Gisela A. Bansod, Yogesh D. Schulte, Friederike A. Müller, Ralph Front Bioeng Biotechnol Bioengineering and Biotechnology Bone remodeling is regulated by the interaction between different cells and tissues across many spatial and temporal scales. Notably, in silico models are regarded as powerful tools to further understand the signaling pathways that regulate this intricate spatial cellular interplay. To this end, we have established a 3D multiscale micro-multiphysics agent-based (micro-MPA) in silico model of trabecular bone remodeling using longitudinal in vivo data from the sixth caudal vertebra (CV6) of PolgA((D257A/D257A)) mice, a mouse model of premature aging. Our in silico model includes a variety of cells as single agents and receptor-ligand kinetics, mechanomics, diffusion and decay of cytokines which regulate the cells’ behavior. We highlighted its capabilities by simulating trabecular bone remodeling in the CV6 of five mice over 4 weeks and we evaluated the static and dynamic morphometry of the trabecular bone microarchitecture. Based on the progression of the average trabecular bone volume fraction (BV/TV), we identified a configuration of the model parameters to simulate homeostatic trabecular bone remodeling, here named basal. Crucially, we also produced anabolic, anti-anabolic, catabolic and anti-catabolic responses with an increase or decrease by one standard deviation in the levels of osteoprotegerin (OPG), receptor activator of nuclear factor kB ligand (RANKL), and sclerostin (Scl) produced by the osteocytes. Our results showed that changes in the levels of OPG and RANKL were positively and negatively correlated with the BV/TV values after 4 weeks in comparison to basal levels, respectively. Conversely, changes in Scl levels produced small fluctuations in BV/TV in comparison to the basal state. From these results, Scl was deemed to be the main driver of equilibrium while RANKL and OPG were shown to be involved in changes in bone volume fraction with potential relevance for age-related bone features. Ultimately, this micro-MPA model provides valuable insights into how cells respond to their local mechanical environment and can help to identify critical pathways affected by degenerative conditions and ageing. Frontiers Media S.A. 2023-03-02 /pmc/articles/PMC10017748/ /pubmed/36937760 http://dx.doi.org/10.3389/fbioe.2023.1091294 Text en Copyright © 2023 Boaretti, Marques, Ledoux, Singh, Kendall, Wehrle, Kuhn, Bansod, Schulte and Müller. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Bioengineering and Biotechnology Boaretti, Daniele Marques, Francisco C. Ledoux, Charles Singh, Amit Kendall, Jack J. Wehrle, Esther Kuhn, Gisela A. Bansod, Yogesh D. Schulte, Friederike A. Müller, Ralph Trabecular bone remodeling in the aging mouse: A micro-multiphysics agent-based in silico model using single-cell mechanomics |
title | Trabecular bone remodeling in the aging mouse: A micro-multiphysics agent-based in silico model using single-cell mechanomics |
title_full | Trabecular bone remodeling in the aging mouse: A micro-multiphysics agent-based in silico model using single-cell mechanomics |
title_fullStr | Trabecular bone remodeling in the aging mouse: A micro-multiphysics agent-based in silico model using single-cell mechanomics |
title_full_unstemmed | Trabecular bone remodeling in the aging mouse: A micro-multiphysics agent-based in silico model using single-cell mechanomics |
title_short | Trabecular bone remodeling in the aging mouse: A micro-multiphysics agent-based in silico model using single-cell mechanomics |
title_sort | trabecular bone remodeling in the aging mouse: a micro-multiphysics agent-based in silico model using single-cell mechanomics |
topic | Bioengineering and Biotechnology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017748/ https://www.ncbi.nlm.nih.gov/pubmed/36937760 http://dx.doi.org/10.3389/fbioe.2023.1091294 |
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