التفاصيل البيبلوغرافية
| العنوان: |
Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss |
| المؤلفون: |
Daniel Hipps, Anna L. M. Smith, David J. Deehan, Amy K. Reeve, Ella P. Dennis, Carla Bradshaw, Laura C. Greaves, Douglass M. Turnbull, Alex Laude, Philip F. Dobson, Craig Stamp |
| المصدر: |
Scientific Reports
Scientific Reports, Vol 10, Iss 1, Pp 1-14 (2020) |
| مصطلحات موضوعية: |
0301 basic medicine, Male, Aging, Osteoclasts, lcsh:Medicine, Cell Count, 02 engineering and technology, Matrix (biology), Mice, Bone Density, Osteogenesis, Femur, lcsh:Science, Bone mineral, Mice, Knockout, Multidisciplinary, Chemistry, Osteoblast, 021001 nanoscience & nanotechnology, Resorption, DNA Polymerase gamma, Mitochondria, medicine.anatomical_structure, Mitochondrial respiratory chain, Mechanisms of disease, Female, 0210 nano-technology, medicine.medical_specialty, Mitochondrial DNA, congenital, hereditary, and neonatal diseases and abnormalities, DNA, Mitochondrial, Article, Electron Transport Complex IV, 03 medical and health sciences, Calcification, Physiologic, Osteoclast, Internal medicine, Physical Conditioning, Animal, medicine, Animals, Humans, Bone Resorption, Bone, Electron Transport Complex I, Osteoblasts, lcsh:R, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, Ageing, Mutation, Osteoporosis, lcsh:Q |
| 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 PolgAmut/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 PolgAmut/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 PolgAmut/mut mice compared with wild-type mice. In vitro assays demonstrated severely impaired mineralised matrix formation and increased osteoclast resorption by PolgAmut/mut cells. Finally, application of an exercise intervention to a subset of PolgAmut/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. |
| اللغة: |
English |
| تدمد: |
2045-2322 |
| DOI: |
10.1038/s41598-020-68566-2 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::305964c1935340c4eb162267eb9bb280 |
| Rights: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....305964c1935340c4eb162267eb9bb280 |
| قاعدة البيانات: |
OpenAIRE |