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Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss
The pathogenesis of declining bone mineral density, a universal feature of ageing, is not fully understood. Somatic mitochondrial DNA (mtDNA) mutations accumulate with age in human tissues and mounting evidence suggests that they may be integral to the ageing process. To explore the potential effect...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363892/ https://www.ncbi.nlm.nih.gov/pubmed/32669663 http://dx.doi.org/10.1038/s41598-020-68566-2 |
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author | Dobson, Philip F. Dennis, Ella P. Hipps, Daniel Reeve, Amy Laude, Alex Bradshaw, Carla Stamp, Craig Smith, Anna Deehan, David J. Turnbull, Doug M. Greaves, Laura C. |
author_facet | Dobson, Philip F. Dennis, Ella P. Hipps, Daniel Reeve, Amy Laude, Alex Bradshaw, Carla Stamp, Craig Smith, Anna Deehan, David J. Turnbull, Doug M. Greaves, Laura C. |
author_sort | Dobson, Philip F. |
collection | PubMed |
description | The pathogenesis of declining bone mineral density, a universal feature of ageing, is not fully understood. Somatic mitochondrial DNA (mtDNA) mutations accumulate with age in human tissues and mounting evidence suggests that they may be integral to the ageing process. To explore the potential effects of mtDNA mutations on bone biology, we compared bone microarchitecture and turnover in an ageing series of wild type mice with that of the PolgA(mut/mut) mitochondrial DNA ‘mutator’ mouse. In vivo analyses showed an age-related loss of bone in both groups of mice; however, it was significantly accelerated in the PolgA(mut/mut) mice. This accelerated rate of bone loss is associated with significantly reduced bone formation rate, reduced osteoblast population densities, increased osteoclast population densities, and mitochondrial respiratory chain deficiency in osteoblasts and osteoclasts in PolgA(mut/mut) mice compared with wild-type mice. In vitro assays demonstrated severely impaired mineralised matrix formation and increased osteoclast resorption by PolgA(mut/mut) cells. Finally, application of an exercise intervention to a subset of PolgA(mut/mut) mice showed no effect on bone mass or mineralised matrix formation in vitro. Our data demonstrate that mitochondrial dysfunction, a universal feature of human ageing, impairs osteogenesis and is associated with accelerated bone loss. |
format | Online Article Text |
id | pubmed-7363892 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-73638922020-07-17 Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss Dobson, Philip F. Dennis, Ella P. Hipps, Daniel Reeve, Amy Laude, Alex Bradshaw, Carla Stamp, Craig Smith, Anna Deehan, David J. Turnbull, Doug M. Greaves, Laura C. Sci Rep Article The pathogenesis of declining bone mineral density, a universal feature of ageing, is not fully understood. Somatic mitochondrial DNA (mtDNA) mutations accumulate with age in human tissues and mounting evidence suggests that they may be integral to the ageing process. To explore the potential effects of mtDNA mutations on bone biology, we compared bone microarchitecture and turnover in an ageing series of wild type mice with that of the PolgA(mut/mut) mitochondrial DNA ‘mutator’ mouse. In vivo analyses showed an age-related loss of bone in both groups of mice; however, it was significantly accelerated in the PolgA(mut/mut) mice. This accelerated rate of bone loss is associated with significantly reduced bone formation rate, reduced osteoblast population densities, increased osteoclast population densities, and mitochondrial respiratory chain deficiency in osteoblasts and osteoclasts in PolgA(mut/mut) mice compared with wild-type mice. In vitro assays demonstrated severely impaired mineralised matrix formation and increased osteoclast resorption by PolgA(mut/mut) cells. Finally, application of an exercise intervention to a subset of PolgA(mut/mut) mice showed no effect on bone mass or mineralised matrix formation in vitro. Our data demonstrate that mitochondrial dysfunction, a universal feature of human ageing, impairs osteogenesis and is associated with accelerated bone loss. Nature Publishing Group UK 2020-07-15 /pmc/articles/PMC7363892/ /pubmed/32669663 http://dx.doi.org/10.1038/s41598-020-68566-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Dobson, Philip F. Dennis, Ella P. Hipps, Daniel Reeve, Amy Laude, Alex Bradshaw, Carla Stamp, Craig Smith, Anna Deehan, David J. Turnbull, Doug M. Greaves, Laura C. Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss |
title | Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss |
title_full | Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss |
title_fullStr | Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss |
title_full_unstemmed | Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss |
title_short | Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss |
title_sort | mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363892/ https://www.ncbi.nlm.nih.gov/pubmed/32669663 http://dx.doi.org/10.1038/s41598-020-68566-2 |
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