Evidence map›Paper›PMID 35619053›Full record

ArticleGenes & nutrition2022

Early life vitamin D depletion and mechanical loading determine methylation changes in the RUNX2, RXRA, and osterix promoters in mice.

Nevena Krstic, Nick Bishop, Beth Curtis, Cyrus Cooper, Nick Harvey, Karen Lilycrop, Robert Murray, Robert Owen, Gwen Reilly, Tim Skerry and 1 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Genes & nutrition, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06509776 (Early Life Determinants of Skeletal Maturation and Endocrine Health in Young Adults - A Nationwide Birth Cohort Study), which is not on this map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06509776 enrolling by invitationnot on this mapstarted 2024, after this paper: background citation

Early Life Determinants of Skeletal Maturation and Endocrine Health in Young Adults - A Nationwide Birth Cohort Study

TypeobservationalSponsorHolbaek SygehusRan2024 to 2031Enrolled2,000ConditionsOsteoporosis, Sarcopenia, Obesity, Cardiovascular Diseases
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Hypomethylation of theInternational journal of molecular sciences · 2024
    Article
  5. Article
  6. Micronutrient regulation of the DNA methylome.Frontiers in epigenetics and epigenomics · 2024
    Review
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Nevena KrsticBiological Sciences and NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK.
Nick BishopDepartment of Oncology & Metabolism, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, UK.
Beth CurtisMRC Lifecourse Epidemiology Unit, Southampton General Hospital, University of Southampton, Southampton, UK.
Cyrus CooperMRC Lifecourse Epidemiology Unit, Southampton General Hospital, University of Southampton, Southampton, UK.
Nick HarveyMRC Lifecourse Epidemiology Unit, Southampton General Hospital, University of Southampton, Southampton, UK.
Karen LilycropBiological Sciences and NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK.
Robert MurrayBiological Sciences and NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK.
Robert OwenDepartment of Materials Science and Engineering, Kroto Research Institute, The University of Sheffield, Sheffield, UK.
Gwen ReillyDepartment of Materials Science and Engineering, Kroto Research Institute, The University of Sheffield, Sheffield, UK.
Tim SkerryDepartment of Oncology & Metabolism, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, UK.
Steph BorgDepartment of Oncology & Metabolism, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, UK. s.borg@sheffield.ac.uk.
University of Sheffield · GBUniversity of Southampton · GBUniversity Hospital Southampton NHS Foundation Trust · GB

Funding

Medical Research Council G0400491Medical Research Council MC_PC_21000Medical Research Council MC_PC_21001Medical Research Council MC_PC_21003Medical Research Council MC_PC_21022Medical Research Council MC_U147585819Medical Research Council MC_U147585824Medical Research Council MC_U147585827Medical Research Council MC_UU_12011/1Medical Research Council MR/L002191/1Versus Arthritis 21231Wellcome Trust 201222/Z/16/Z
6 · The paper itself

Abstract

backgroundEarly 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.

resultsMechanical 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.

conclusionsWe 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.

Indexed as

BoneEpigeneticsMechanical loadingMethylationOsterixRXRAVitamin D

Identifiers

PMID35619053
PMCPMC9137183
OpenAlexW4281559827

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.