Academic Journal
Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss
| العنوان: | Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss |
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| المؤلفون: | 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. |
| المصدر: | Scientific Reports ; volume 10, issue 1 ; ISSN 2045-2322 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2020 |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41598-020-68566-2 |
| الاتاحة: | http://dx.doi.org/10.1038/s41598-020-68566-2 https://www.nature.com/articles/s41598-020-68566-2.pdf https://www.nature.com/articles/s41598-020-68566-2 |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.F7959E5A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-020-68566-2 |
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