Evidence map›Paper›PMID 24877565›Full record

ArticleMolecular endocrinology (Baltimore, Md.)2014

The osteoblast to osteocyte transition: epigenetic changes and response to the vitamin D3 hormone.

Hillary C St John, Kathleen A Bishop, Mark B Meyer, Nancy A Benkusky, Ning Leng, Christina Kendziorski, Lynda F Bonewald, J Wesley Pike

Open access · bronzeAbstract read
In one paragraph

Article in Molecular endocrinology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 2 pooled it
6.4field-weighted citation impact, top 3% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 129 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Vitamins DFrontiers in immunology · 2022
    Trial
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  15. Positive and Negative Regulators of Sclerostin Expression.International journal of molecular sciences · 2022
    Review
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  17. Article
  18. Article
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  20. Review

1 more citing papers are in PubMed but not listed here.

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

8 authors at 2 institutions in 1 country.

Hillary C St JohnDepartment of Biochemistry (H.C.S., K.A.B., M.B.M., N.A.B., J.W.P.) and Department of Biostatistics (N.L., C.K.), University of Wisconsin-Madison, Madison, Wisconsin 53706; and Department of Oral Biology (L.F.B.), School of Dentistry, University of Missouri, Kansas City, Missouri 6410.
Kathleen A Bishop
Mark B Meyer
Nancy A Benkusky
Ning Leng
Christina Kendziorski
Lynda F Bonewald
J Wesley Pike
University of Wisconsin–Madison · USUniversity of Missouri–Kansas City · US

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI AMY TRENTHAM-DIETZ · 1985 to 2026
$142.6M
Institutional Clinical and Translational Science AwardUL1TR000427 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2012 to 2016
$32.2M
INSTITUTIONAL CTSA (UW-MADISON): CLINICAL TRIALSUL1RR025011 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2007 to 2011
$29.5M
Statistical methods for spatial RNA sequencing experimentsR01GM102756 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI KENDZIORSKI, CHRISTINA · 2012 to 2024
$3.8M
Dynamic Mechanisms of Vitamin D-Induced Gene ExpressionR01DK072281 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI PIKE, J WESLEY · 2005 to 2012
$2.6M
Integrative genomics to define osteocyte differentiation, regulation and functionR01AR064424 · NIAMS · UNIVERSITY OF WISCONSIN-MADISON · PI PIKE, J WESLEY · 2014 to 2018
$1.7M
NCATS NIH HHS UL1 TR000427NCI NIH HHS P30 CA014520NCRR NIH HHS UL1 RR025011NCRR NIH HHS UL1RR025011NIAMS NIH HHS R01 AR064424NIDDK NIH HHS DK-072281NIDDK NIH HHS R01 DK072281NIGMS NIH HHS GM102756NIGMS NIH HHS R01 GM102756
6 · The paper itself

Abstract

Osteocytes are derived from osteoblast lineage cells that become progressively embedded in mineralized bone. Development of the osteocytogenic cell line IDG-SW3 has enabled a temporal and mechanistic investigation of this process. Through RNA-sequencing analyses, we show that although substantial changes in gene expression occur during the osteoblast to osteocyte transition, the majority of the transcriptome remains qualitatively osteoblast like. Genes either up-regulated or expressed uniquely in the osteocyte include local and systemic factors such as Sost and Fgf23 as well as genes implicated in neuronal, muscle, vascular, or regulatory function. As assessed by chromatin immunoprecipitation coupled to high-throughput sequencing, numerous changes in epigenetic histone modifications also occur during osteocytogenesis; these are largely qualitative rather than quantitative. Specific epigenetic changes correlate with altered gene expression patterns that are observed during the transition. These genomic changes likely influence the highly restricted transcriptomic response to 1,25(OH)(2)D(3) that occurs during differentiation. VDR binding in osteocytes revealed an extensive cistrome co-occupied by retinoid X receptor and located predominantly at sites distal to regulated genes. Although sites of VDR binding were apparent near many 1,25(OH)(2)D(3)-regulated genes, the expression of others adjacent to VDR-binding sites were unaffected; lack of VDR binding was particularly prevalent at down-regulated genes. Interestingly, 1,25(OH)(2)D(3) was found to induce the Boc and Cdon coreceptors that are active in hedgehog signaling in osteocytes. We conclude that osteocytogenesis is accompanied by changes in gene expression that may be driven by both genetic and epigenetic components. These changes are likely responsible for the osteocyte phenotype and may contribute to reduced sensitivity to 1,25(OH)(2)D(3).

Indexed as

3T3 CellsAdaptor Proteins, Signal TransducingAnimalsBone Density Conservation AgentsCalcification, PhysiologicCalcitriolCell Adhesion MoleculesCell DifferentiationCell LineChromatin ImmunoprecipitationFibroblast Growth Factor-23Fibroblast Growth FactorsGene Expression RegulationGlycoproteinsImmunoglobulin GIntercellular Signaling Peptides and ProteinsAdaptor Proteins, Signal TransducingBoc protein, mouseBone Density Conservation AgentsCalcitriolCdon protein, mouseCell Adhesion MoleculesFgf23 protein, mouseFibroblast Growth Factor-23Fibroblast Growth FactorsGlycoproteinsImmunoglobulin GIntercellular Signaling Peptides and ProteinsReceptors, CalcitriolReceptors, Cell SurfaceRetinoid X ReceptorsSost protein, mouse

Identifiers

PMID24877565
PMCPMC5414828
OpenAlexW2008790622

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.