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

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

Scientific reports (2020-07-17)
Philip F Dobson, Ella P Dennis, Daniel Hipps, Amy Reeve, Alex Laude, Carla Bradshaw, Craig Stamp, Anna Smith, David J Deehan, Doug M Turnbull, Laura 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 demonstrate that mitochondrial dysfunction, a universal feature of human ageing, impairs osteogenesis and is associated with accelerated bone loss.

MATERIALS
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Product Description

Sigma-Aldrich
Fast Blue RR Salt, crystalline
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10 μg
1 Estimated to ship on February 28, 2025
$398.00
25 μg
1 Estimated to ship on February 28, 2025
$790.00
50 μg
1 Estimated to ship on February 28, 2025
$1,200.00
Sigma-Aldrich
Ser-Phe-Leu-Leu-Arg-Asn-Pro-Asn-Asp-Lys-Tyr-Glu-Pro-Phe, ≥97% (HPLC)
Sign Into View Organizational & Contract Pricing
SKUPack SizeAvailabilityPriceQuantity
10 μg
1 Estimated to ship on February 28, 2025
$398.00
25 μg
1 Estimated to ship on February 28, 2025
$790.00
50 μg
1 Estimated to ship on February 28, 2025
$1,200.00