Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss.

Scientific Reports
Philip F DobsonLaura C Greaves

Abstract

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 demons...Continue Reading

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Citations

Nov 22, 2020·Bone·Austin P Hensley, Audrey McAlinden
Nov 12, 2020·International Journal of Molecular Sciences·Tian ZhaoTimothy E Shutt
Apr 4, 2021·International Journal of Molecular Sciences·Abhishek Chandra, Jyotika Rajawat
Jun 10, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Kenneth Kin Leung KwanKarl Wah Keung Tsim
Aug 26, 2021·Organogenesis·Steven F DobrowolskiHarry C Blair

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Methods Mentioned

BETA
dissection
light microscopy

Software Mentioned

Rstudio
GraphPad
Prism
Volocity
Matlab
Imaris
NIS
elements

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