Early life vitamin D depletion and mechanical loading determine methylation changes in the RUNX2, RXRA, and osterix promoters in mice.
Early life vitamin D depletion and mechanical loading determine methylation changes in the RUNX2, RXRA, and osterix promoters in mice.
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DOI：
10.1186/s12263-022-00711-0
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发表时间：
2022-05-26
影响因子：
3.5
通讯作者：
Borg, Steph
中科院分区：
文献类型：
--
作者：
Krstic, Nevena;Bishop, Nick;Curtis, Beth;Cooper, Cyrus;Harvey, Nick;Lilycrop, Karen;Murray, Robert;Owen, Robert;Reilly, Gwen;Skerry, Tim;Borg, Steph
早期维生素D暴露与后期骨骼健康有关，妊娠期母体维生素D状况与新生儿骨量相关。MAVIDOS研究表明，维生素D补充剂可降低RXRA DNA甲基化。暴露于早期维生素D缺乏症的小鼠响应于机械负荷具有降低的骨量和骨累积。使用这些小鼠的时间表，我们研究了饮食和机械负荷对骨生长和发育重要的遗传位点的启动子的DNA甲基化及其与骨强度的关系的影响。小鼠胸腺的机械负荷导致RXRA DNA甲基化的减少。早期维生素D缺乏与这些骨骼中osterix和Runx2的甲基化改变有关。胫骨强度也被证明与维生素D受体（VDR）、ostrix和RXRA基因的CpG中DNA甲基化状态的变化相关。我们首次表明，骨的机械负荷和早期维生素D缺乏导致维生素D和成骨细胞分化途径中关键基因的表观基因组发生变化。
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. 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. 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.
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影响因子：
6.1
作者：
Gomathi, K.;Akshaya, N.;Selvamurugan, N.
通讯作者：
Selvamurugan, N.
影响因子：
4
作者：
Sinha, Krishna M.;Zhou, Xin
通讯作者：
Zhou, Xin
影响因子：
64.8
作者：
Ng, Sheau-Fang;Lin, Ruby C. Y.;Morris, Margaret J.
通讯作者：
Morris, Margaret J.
影响因子：
168.9
作者：
Javaid, MK;Crozier, SR;Cooper, C
通讯作者：
Cooper, C
DOI：
10.1073/pnas.0705667104
发表时间：
2007-07-31
影响因子：
11.1
作者：
Gluckman, Peter D.;Lillycrop, Karen A.;Hanson, Mark A.
通讯作者：
Hanson, Mark A.