Bioenergetic programs of cancellous and cortical bone are distinct and differ with age and mechanical loading

Mechanical loading induces bone formation in young rodents, but mechanoresponsiveness is reduced with age. Glycolytic activity and mitochondrial dysfunction increase with age and may change bone mechanotransduction. To evaluate load-induced changes to bioenergetic activity in young and adult animals, we loaded the tibia of 10-wk and 26-wk female mice and examined transcriptomic responses at the mid-diaphysis, metaphyseal cortical shell, and cancellous core. Across all biological processes, oxidative phosphorylation and mitochondrial pathways were most often enriched with loading and had opposite enrichment in young and adult animals. Following loading, young animals had temporally-coordinated differential expression of mitochondrial-associated genes, with greatest expression at the mid-diaphysis. In adults, bioenergetic gene expression was lower compared to young animals. Overall design: Comparative gene expression profiling of RNA-seq data for bone samples from loaded limbs and contralateral control limbs of 10wk and 26 wk old female C57Bl6 mice. At various time points following tibial loading, the cancellous core and 2 cortical segments (metaphyseal cortical shell and mid-diaphysis) were collected. Differential expression was assessed at each cortical location at 1-h, 3-h, and 24-h following a single loading session. To evaluate long term time points, a final group received 5 consecutive days of loading with euthanasia on the eighth day following the first loading session.