Evidence map›Paper›PMID 23251594›Full record

ArticlePloS one2012

Mechanical strain downregulates C/EBPβ in MSC and decreases endoplasmic reticulum stress.

Maya Styner, Mark B Meyer, Kornelia Galior, Natasha Case, Zhihui Xie, Buer Sen, William R Thompson, John Wesley Pike, Janet Rubin

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.5field-weighted citation impact, top 20% 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

22 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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  6. Review
  7. Article
  8. Review
  9. Review
  10. Exercise Degrades Bone in Caloric Restriction, Despite Suppression of Marrow Adipose Tissue (MAT).Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020
    Article
  11. Review
  12. Actin up in the Nucleus: Regulation of Actin Structures Modulates Mesenchymal Stem Cell Differentiation.Transactions of the American Clinical and Climatological Association · 2017
    Article
  13. Article
  14. Review
  15. The increasingly complex regulation of adipocyte differentiation.Experimental biology and medicine (Maywood, N.J.) · 2016
    Review
  16. Exercise Regulation of Marrow Adipose Tissue.Frontiers in endocrinology · 2016
    Review
  17. Article
  18. Article
  19. Article
  20. Article
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

9 authors at 2 institutions in 1 country.

Maya StynerDepartment of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA. mstyner@med.unc.edu
Mark B Meyer
Kornelia Galior
Natasha Case
Zhihui Xie
Buer Sen
William R Thompson
John Wesley Pike
Janet Rubin
University of North Carolina at Chapel Hill · USUniversity of Wisconsin–Madison · US

Funding

UNC BIRCWH CAREER DEVELOPMENT PROGRAMK12HD001441 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BOGGESS, KIM A · 2000 to 2019
$9.3M
ELECTRIC FIELD ATTENUATION OF OSTEOCLAST FORMATIONR01AR042360 · NIAMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RUBIN, JANET E · 1993 to 2013
$2.8M
Dynamic Mechanisms of Vitamin D-Induced Gene ExpressionR01DK072281 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI PIKE, J WESLEY · 2005 to 2012
$2.6M
Mechanical Control of Mesenchymal Stem Cell Lineage AllocationR01AR056655 · NIAMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RUBIN, JANET E · 2010 to 2014
$1.4M
Role of C/EBPbeta in mechanical regulation of MSC potentialK08AR062097 · NIAMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI STYNER, MAYA SHALEV · 2012 to 2016
$651k
Biophysical regulation of bone remodelingR56AR042360 · NIAMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RUBIN, JANET E · 2008 to 2008
$289k
NIAMS NIH HHS 1K08AR062097NIAMS NIH HHS AR042360NIAMS NIH HHS AR05665NIAMS NIH HHS K08 AR062097NIAMS NIH HHS R01 AR042360NIAMS NIH HHS R01 AR056655NIAMS NIH HHS R56 AR042360NICHD NIH HHS 5K12HD001441NICHD NIH HHS K12 HD001441NIDDK NIH HHS DK072281NIDDK NIH HHS R01 DK072281
6 · The paper itself

Abstract

Exercise prevents marrow mesenchymal stem cell (MSC) adipogenesis, reversing trends that accompany aging and osteoporosis. Mechanical input, the in-vitro analogue to exercise, limits PPARγ expression and adipogenesis in MSC. We considered whether C/EBPβ might be mechanoresponsive as it is upstream to PPARγ, and also is known to upregulate endoplasmic reticulum (ER) stress. MSC (C3H10T1/2 pluripotent cells as well as mouse marrow-derived MSC) were cultured in adipogenic media and a daily mechanical strain regimen was applied. We demonstrate herein that mechanical strain represses C/EBPβ mRNA (0.6-fold ±0.07, p<0.05) and protein (0.4-fold ±0.1, p<0.01) in MSC. SiRNA silencing of β-catenin prevented mechanical repression of C/EBPβ. C/EBPβ overexpression did not override strain's inhibition of adipogenesis, which suggests that mechanical control of C/EBPβ is not the primary site at which adipogenesis is regulated. Mechanical inhibition of C/EBPβ, however, might be critical for further processes that regulate MSC health. Indeed, overexpression of C/EBPβ in MSC induced ER stress evidenced by a dose-dependent increase in the pro-apoptotic CHOP (protein 4-fold ±0.5, p<0.05) and a threshold reduction in the chaperone BiP (protein 0.6-fold ±0.1, p = 0.2; mRNA 0.3-fold ±0.1, p<0.01). ChIP-seq demonstrated a significant association between C/EBPβ and both CHOP and BiP genes. The strain regimen, in addition to decreasing C/EBPβ mRNA (0.5-fold ±0.09, p<0.05), expanded ER capacity as measured by an increase in BiP mRNA (2-fold ±0.2, p<0.05) and protein. Finally, ER stress induced by tunicamycin was ameliorated by mechanical strain as demonstrated by decreased C/EBPβ, increased BiP and decreased CHOP protein expression. Thus, C/EBPβ is a mechanically responsive transcription factor and its repression should counter increases in marrow fat as well as improve skeletal resistance to ER stress.

Indexed as

Down-RegulationEndoplasmic Reticulum StressStress, MechanicalAdipogenesisAnimalsCCAAT-Enhancer-Binding Protein-betaMesenchymal Stem CellsMiceMice, Inbred C57BLTunicamycinCCAAT-Enhancer-Binding Protein-betaTunicamycin

Identifiers

PMID23251594
PMCPMC3520924
OpenAlexW2016846918

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.