Evidence map›Paper›PMID 24440782›Full record

ArticleGene2014

Stratified control of IGF-I expression by hypoxia and stress hormones in osteoblasts.

Thomas L McCarthy, Zhong Yun, Joseph A Madri, Michael Centrella

Open access · greenAbstract read
In one paragraph

Article in Gene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

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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

4 authors at 1 institution in 1 country.

Thomas L McCarthyYale University School of Medicine, Department of Surgery, New Haven, CT 06520-8041, USA; Yale University School of Medicine, Department of Pathology, New Haven, CT 06520-8023, USA. Electronic address: thomas.mccarthy@yale.edu.
Zhong YunYale University School of Medicine, Department of Therapeutic Radiology, New Haven, CT 06520-8040, USA.
Joseph A MadriYale University School of Medicine, Department of Pathology, New Haven, CT 06520-8023, USA.
Michael CentrellaYale University School of Medicine, Department of Surgery, New Haven, CT 06520-8041, USA; Yale University School of Medicine, Department of Pathology, New Haven, CT 06520-8023, USA. Electronic address: michael.centrella@yale.edu.
Yale University · US

Funding

YALE CORE CENTER FOR MUSCULOSKELETAL DISORDERSP30AR046032 · NIAMS · YALE UNIVERSITY · PI HOROWITZ, MARK C · 1999 to 2013
$9.0M
CONTROL OF TGFB RECEPTOR EXPRESSION IN BONER01AR039201 · NIAMS · YALE UNIVERSITY · PI CENTRELLA, MICHAEL · 1995 to 2007
$2.6M
Epigenetic Regulation in Hypoxic Cancer CellsR01CA148996 · NCI · YALE UNIVERSITY · PI GLAZER, PETER M, YUN, ZHONG · 2010 to 2014
$1.6M
Role of Hypoxia in the regulation of cancer cell differentiationR01CA125021 · NCI · YALE UNIVERSITY · PI YUN, ZHONG · 2007 to 2011
$1.6M
Regulators of Osteoblast Protein Synthesis InitiationR21AR062764 · NIAMS · YALE UNIVERSITY · PI CENTRELLA, MICHAEL, MCCARTHY, THOMAS LEO · 2012 to 2013
$324k
BONE COLLAGEN PRODUCTION BY BONE-DERIVED TGFBR29AR039201 · NIAMS · YALE UNIVERSITY · PI CENTRELLA, MICHAEL · 1988 to 1992
–
NCI NIH HHS CA125021NCI NIH HHS CA148996NCI NIH HHS R01 CA125021NCI NIH HHS R01 CA148996NIAMS NIH HHS AR046032NIAMS NIH HHS AR062764NIAMS NIH HHS AR39201NIAMS NIH HHS R01 AR039201NIAMS NIH HHS R21 AR062764NINDS NIH HHS NS00344738
6 · The paper itself

Abstract

Bone cells respond to the integrated effects of local and systemic regulation. Here we show that hypoxia and the stress hormones PGE2 and glucocorticoid interact in complex ways in osteoblasts, converging on insulin like growth factor I (IGF-I) expression. Whereas hypoxia alone rapidly increased transcription factor HIF activity, it suppressed DNA synthesis, had no significant effects on protein synthesis or alkaline phosphatase activity, and drove discrete changes in a panel of osteoblast mRNAs. Notably, hypoxia increased expression of the acute phase response transcription factor C/EBPδ which can induce IGF-I in response to PGE2, but conversely prevented the stimulatory effect of PGE2 on IGF-I mRNA. However, unlike its effect on C/EBPδ, hypoxia suppressed expression of the obligate osteoblast transcription factor Runx2, which can activate an upstream response element in the IGF-I gene promoter. Hypoxic inhibition of IGF-I and Runx2 were enforced by glucocorticoid, and continued with prolonged exposure. Our studies thus reveal that IGF-I expression is stratified by two critical transcriptional elements in osteoblasts, which are resolved by the individual and combined effects of hypoxic stress and stress hormones. In so doing, hypoxia suppresses Runx2, limits the enhancing influence of PGE2, and interacts with glucocorticoid to reduce IGF-I expression by osteoblasts.

Indexed as

Alkaline PhosphataseAnimalsCCAAT-Enhancer-Binding Protein-deltaCell HypoxiaCells, CulturedCore Binding Factor Alpha 1 SubunitDinoprostoneDNADNA ReplicationGene Expression RegulationHydrocortisoneInsulin-Like Growth Factor IOsteoblastsOxygenPromoter Regions, GeneticProtein BiosynthesisAlkaline PhosphataseCCAAT-Enhancer-Binding Protein-deltaCebpd protein, ratCore Binding Factor Alpha 1 SubunitDinoprostoneDNAHydrocortisoneInsulin-Like Growth Factor IOxygenRNA, MessengerRunx2 protein, ratC/EBPGlucocorticoidHIFPGE2Runx2

Identifiers

PMID24440782
PMCPMC4316208
OpenAlexW2060391348

What OpenQuestion holds

Textmetadata
LicenceTDM
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.