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Oxaloacetate enhances and accelerates regeneration in young mice by promoting proliferation and mineralization
Cell metabolism coordinates the biochemical reactions that produce carbon and ATP in order for the cell to proliferate, differentiate, and respond to environmental changes. Cell type determines metabolic demand, so proliferating skeletal progenitors and differentiated osteoblasts exhibit different l...
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/PMC9999028/ https://www.ncbi.nlm.nih.gov/pubmed/36910154 http://dx.doi.org/10.3389/fcell.2023.1117836 |
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author | Jaramillo, Josue Taylor, Caroline McCarley, Rachel Berger, Melissa Busse, Emily Sammarco, Mimi C. |
author_facet | Jaramillo, Josue Taylor, Caroline McCarley, Rachel Berger, Melissa Busse, Emily Sammarco, Mimi C. |
author_sort | Jaramillo, Josue |
collection | PubMed |
description | Cell metabolism coordinates the biochemical reactions that produce carbon and ATP in order for the cell to proliferate, differentiate, and respond to environmental changes. Cell type determines metabolic demand, so proliferating skeletal progenitors and differentiated osteoblasts exhibit different levels of cell metabolism. Limb regeneration is an energetically demanding process that involves multiple types of tissues and cell functions over time. Dysregulation of cell metabolism in aged mice results in impaired regeneration, a defect that can be rescued in part by the administration of oxaloacetate (OAA). A better understanding of how cell metabolism regulates regeneration in general, and how these changes can be modulated to benefit potential regenerative strategies in the future is needed. Here we sought to better understand the effects of OAA on young mice and determine whether the same mechanism could be tapped to improve regeneration without an aged-defect. We also asked which dosing time periods were most impactful for promoting regenerative outcomes, and whether these effects were sustained after dosing was stopped. Consistent with our findings in aged mice we found that OAA enhanced regeneration by accelerating bone growth, even beyond control measures, by increasing trabecular thickness, decreasing trabecular spacing, and improving the patterning by decreasing the taper, making the regenerated bone more like an unamputated digit. Our data suggests that the decrease in spacing, an improvement over aged mice, may be due to a decrease in hypoxia-driven vasculature. Our findings suggest that OAA, and similar metabolites, may be a strong tool to promote regenerative strategies and investigate the mechanisms that link cell metabolism and regeneration. |
format | Online Article Text |
id | pubmed-9999028 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99990282023-03-11 Oxaloacetate enhances and accelerates regeneration in young mice by promoting proliferation and mineralization Jaramillo, Josue Taylor, Caroline McCarley, Rachel Berger, Melissa Busse, Emily Sammarco, Mimi C. Front Cell Dev Biol Cell and Developmental Biology Cell metabolism coordinates the biochemical reactions that produce carbon and ATP in order for the cell to proliferate, differentiate, and respond to environmental changes. Cell type determines metabolic demand, so proliferating skeletal progenitors and differentiated osteoblasts exhibit different levels of cell metabolism. Limb regeneration is an energetically demanding process that involves multiple types of tissues and cell functions over time. Dysregulation of cell metabolism in aged mice results in impaired regeneration, a defect that can be rescued in part by the administration of oxaloacetate (OAA). A better understanding of how cell metabolism regulates regeneration in general, and how these changes can be modulated to benefit potential regenerative strategies in the future is needed. Here we sought to better understand the effects of OAA on young mice and determine whether the same mechanism could be tapped to improve regeneration without an aged-defect. We also asked which dosing time periods were most impactful for promoting regenerative outcomes, and whether these effects were sustained after dosing was stopped. Consistent with our findings in aged mice we found that OAA enhanced regeneration by accelerating bone growth, even beyond control measures, by increasing trabecular thickness, decreasing trabecular spacing, and improving the patterning by decreasing the taper, making the regenerated bone more like an unamputated digit. Our data suggests that the decrease in spacing, an improvement over aged mice, may be due to a decrease in hypoxia-driven vasculature. Our findings suggest that OAA, and similar metabolites, may be a strong tool to promote regenerative strategies and investigate the mechanisms that link cell metabolism and regeneration. Frontiers Media S.A. 2023-02-24 /pmc/articles/PMC9999028/ /pubmed/36910154 http://dx.doi.org/10.3389/fcell.2023.1117836 Text en Copyright © 2023 Jaramillo, Taylor, McCarley, Berger, Busse and Sammarco. 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 | Cell and Developmental Biology Jaramillo, Josue Taylor, Caroline McCarley, Rachel Berger, Melissa Busse, Emily Sammarco, Mimi C. Oxaloacetate enhances and accelerates regeneration in young mice by promoting proliferation and mineralization |
title | Oxaloacetate enhances and accelerates regeneration in young mice by promoting proliferation and mineralization |
title_full | Oxaloacetate enhances and accelerates regeneration in young mice by promoting proliferation and mineralization |
title_fullStr | Oxaloacetate enhances and accelerates regeneration in young mice by promoting proliferation and mineralization |
title_full_unstemmed | Oxaloacetate enhances and accelerates regeneration in young mice by promoting proliferation and mineralization |
title_short | Oxaloacetate enhances and accelerates regeneration in young mice by promoting proliferation and mineralization |
title_sort | oxaloacetate enhances and accelerates regeneration in young mice by promoting proliferation and mineralization |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9999028/ https://www.ncbi.nlm.nih.gov/pubmed/36910154 http://dx.doi.org/10.3389/fcell.2023.1117836 |
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