Evidence map›Paper›PMID 22049075›Full record

ArticleThe Journal of biological chemistry2012

Loading-related regulation of transcription factor EGR2/Krox-20 in bone cells is ERK1/2 protein-mediated and prostaglandin, Wnt signaling pathway-, and insulin-like growth factor-I axis-dependent.

Gul Zaman, Andrew Sunters, Gabriel L Galea, Behzad Javaheri, Leanne K Saxon, Alaa Moustafa, Victoria J Armstrong, Joanna S Price, Lance E Lanyon

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

24 citing papers in PubMed, 35 citations in OpenAlex.

  1. Trial
  2. mBio · 2025
    Article
  3. Article
  4. Deletion of TECRL promotes skeletal muscle repair by up-regulating EGR2.Proceedings of the National Academy of Sciences of the United States of America · 2024
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  19. Age-related impairment of bones' adaptive response to loading in mice is associated with sex-related deficiencies in osteoblasts but no change in osteocytes.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2014
    Article
  20. The anti-diabetic drug metformin does not affect bone mass in vivo or fracture healing.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2013
    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 3 institutions in 2 countries.

Gul ZamanDepartment of Veterinary Basic Sciences, Royal Veterinary College, London, NW1 0TU, United Kingdom. gzaman@rvc.ac.uk
Andrew Sunters
Gabriel L Galea
Behzad Javaheri
Leanne K Saxon
Alaa Moustafa
Victoria J Armstrong
Joanna S Price
Lance E Lanyon
Royal Veterinary College · GBUniversity of Bristol · GBUniversity of Missouri–Kansas City · US

Funding

Wellcome Trust
6 · The paper itself

Abstract

Of the 1,328 genes revealed by microarray to be differentially regulated by disuse, or at 8 h following a single short period of osteogenic loading of the mouse tibia, analysis by predicting associated transcription factors from annotated affinities revealed the transcription factor EGR2/Krox-20 as being more closely associated with more pathways and functions than any other. Real time quantitative PCR confirmed up-regulation of Egr2 mRNA expression by loading of the tibia in vivo. In vitro studies where strain was applied to primary cultures of mouse tibia-derived osteoblastic cells and the osteoblast UMR106 cell line also showed up-regulation of Egr2 mRNA expression. In UMR106 cells, inhibition of β1/β3 integrin function had no effect on strain-related Egr2 expression, but it was inhibited by a COX2-selective antagonist and imitated by exogenous prostaglandin E2 (PGE2). This response to PGE(2) was mediated chiefly through the EP1 receptor and involved stimulation of PKC and attenuation by cAMP/PKA. Neither activators nor inhibitors of nitric oxide, estrogen signaling, or LiCl had any effect on Egr2 mRNA expression, but it was increased by both insulin-like growth factor-1 and high, but not low, dose parathyroid hormone and exogenous Wnt-3a. The increases by strain, PGE2, Wnt-3a, and phorbol 12-myristate 13-acetate were attenuated by inhibition of MEK-1. EGR2 appears to be involved in many of the signaling pathways that constitute early responses of bone cells to strain. These pathways all have multiple functions. Converting their strain-related responses into coherent "instructions" for adaptive (re)modeling is likely to depend upon their contextual activation, suppression, and interaction probably on more than one occasion.

Indexed as

AnimalsBone and BonesCarcinogensCell LineCyclic AMPCyclic AMP-Dependent Protein KinasesCyclooxygenase 2DinoprostoneEarly Growth Response Protein 2FemaleInsulin-Like Growth Factor IIntegrin beta1Integrin beta3MAP Kinase Kinase 1MiceMitogen-Activated Protein Kinase 3CarcinogensCyclic AMPCyclic AMP-Dependent Protein KinasesCyclooxygenase 2DinoprostoneEarly Growth Response Protein 2Egr2 protein, mouseinsulin-like growth factor-1, mouseInsulin-Like Growth Factor IIntegrin beta1Integrin beta3Map2k1 protein, mouseMAP Kinase Kinase 1Mitogen-Activated Protein Kinase 3Nitric OxidePtger1 protein, mousePtgs2 protein, mouseReceptors, Prostaglandin E, EP1 SubtypeRNA, MessengerTetradecanoylphorbol AcetateWnt3A ProteinWnt3a protein, mouse

Identifiers

PMID22049075
PMCPMC3281728
OpenAlexW2159400530

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.