Author:
Krstic Nevena,Bishop Nick,Curtis Beth,Cooper Cyrus,Harvey Nick,Lilycrop Karen,Murray Robert,Owen Robert,Reilly Gwen,Skerry Tim,Borg Steph
Abstract
Abstract
Background
Early life vitamin D exposure is linked to later skeletal health with maternal vitamin D status in pregnancy associated with neonatal bone mass. The MAVIDOS study has demonstrated that vitamin D supplementation leads to reduced RXRA DNA methylation. Mice exposed to early life vitamin D deficiency have reduced bone mass and bone accrual in response to mechanical loading. Using the tibiae of these mice, we have examined the effect of diet and mechanical loading on the DNA methylation of promoters of genetic loci important for bone growth and development and their association with bone strength.
Results
Mechanical loading of mouse tibiae leads to a reduction of RXRA DNA methylation. Early life vitamin D deficiency is associated with altered methylation of osterix and Runx2 in these bones. Tibia strength was also demonstrated to be associated with a change in DNA methylation status in CpGs of the vitamin D receptor (VDR), ostrix, and RXRA genes.
Conclusions
We have shown for the first time that mechanical loading of bone and early life vitamin D deficiency leads to changes in the epigenome of this tissue in key genes in the vitamin D and osteoblast differentiation pathway.
Publisher
Springer Science and Business Media LLC
Subject
Genetics,Endocrinology, Diabetes and Metabolism
Cited by
2 articles.
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