Evidence map›Paper›PMID 25946081›Full record

ArticlePloS one2015

Sexual Dimorphism in MAPK-Activated Protein Kinase-2 (MK2) Regulation of RANKL-Induced Osteoclastogenesis in Osteoclast Progenitor Subpopulations.

Bethany A Herbert, Michael S Valerio, Matthias Gaestel, Keith L Kirkwood

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.4field-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

15 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Roles of Mitogen-Activated Protein Kinases in Osteoclast Biology.International journal of molecular sciences · 2018
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. 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

4 authors at 2 institutions in 2 countries.

Bethany A HerbertDepartment of Oral Health Sciences and the Center for Oral Health Research, Medical University of South Carolina, Charleston, South Carolina, United States of America.
Michael S ValerioDepartment of Oral Health Sciences and the Center for Oral Health Research, Medical University of South Carolina, Charleston, South Carolina, United States of America.
Matthias GaestelInstitute of Biochemistry, Hannover Medical School, Hannover, Germany.
Keith L KirkwoodDepartment of Oral Health Sciences and the Center for Oral Health Research, Medical University of South Carolina, Charleston, South Carolina, United States of America.
Medical University of South Carolina · USMedizinische Hochschule Hannover · DE

Funding

Translational Science Laboratory Shared ResourceP30CA138313 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND N. DUBOIS · 2009 to 2026
$42.7M
T-COHR: Training in Craniofacial and Oral Health ResearchT32DE017551 · NIDCR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI YAO, HAI · 2006 to 2025
$10.3M
Pilot and Feasibility Project ProgramP30GM103331 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI KIRKWOOD, KEITH L · 2012 to 2016
$5.2M
Post-Transcriptional Regulation of Periodontal DiseR01DE021423 · NIDCR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI KIRKWOOD, KEITH L · 2011 to 2015
$2.1M
MUSC FACIL EXPANSION &RENOV: SLE C06RR015455 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND, JOHN R · 2002 to 2002
$2.0M
The Role of MAPK-Activated Protein Kinase 2 in Periodontal DiseaseF30DE024368 · NIDCR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI HARBIN, BETHANY A. · 2014 to 2017
$156k
NCI NIH HHS P30 CA138313NCI NIH HHS P30CA138313NCRR NIH HHS C06 RR015455NCRR NIH HHS C06RR015455NIDCR NIH HHS 5R01DE021423NIDCR NIH HHS F30 DE024368NIDCR NIH HHS F30DE024368NIDCR NIH HHS R01 DE021423NIDCR NIH HHS T32 DE017551NIDCR NIH HHS T32DE017551-05NIGMS NIH HHS P30 GM103331NIGMS NIH HHS P30GM103331
6 · The paper itself

Abstract

Osteoclasts (OCs) are bone-resorptive cells critical for maintaining skeletal integrity through coupled bone turnover. OC differentiation and activation requires receptor activator of NF-kB ligand (RANKL) signaling through the p38 MAPK pathway. However the role of the p38 MAPK substrate, MAPK-activated protein kinase 2 (MK2), is not clearly delineated. Within the bone marrow exists a specific subpopulation of defined osteoclast progenitor cells (dOCPs) with surface expression of B220(-)Gr1(-)CD11b(lo/-)CD115(+) (dOCP(lo/-)). In this study, we isolated dOCPs from male and female mice to determine sex-specific effects of MK2 signaling in osteoclastogenesis (OCgen). Male Mk2(-/-) mice display an increase in the dOCP(lo) cell population when compared to Mk2(+/+) mice, while female Mk2(-/-) and Mk2(+/+ )mice exhibit no difference. Defined OCPs from male and female Mk2(+/+) and Mk2(-/-) bone marrow were treated with macrophage colony stimulation factor (M-CSF) and RANKL cytokines to promote OCgen. RANKL treatment of dOCP(lo) cells stimulated p38 and MK2 phosphorylation. Tartrate-resistant acid phosphatase (TRAP) assays were used to quantify OC number, size, and TRAP enzyme activity post-RANKL stimulation. MK2 signaling was critical for male dOCP(lo) OCgen, yet MK2 signaling regulated OCgen from female dOCP- and CD11b(hi) subpopulations as well. The functional gene, Ctsk, was attenuated in both male and female Mk2(-/-) dOCP(lo)-derived OCs. Conversely, MK2 signaling was only critical for gene expression of pre-OC fusion genes, Oc-stamp andTm7sf4, in male OCgen. Therefore, these data suggest there is a sexual dimorphism in MK2 signaling of OCP subpopulations.

Indexed as

Sex CharacteristicsAcid PhosphataseAnimalsBone Marrow CellsCathepsin KCell DifferentiationCells, CulturedFemaleIntracellular Signaling Peptides and ProteinsIsoenzymesMaleMAP-Kinase-Activated Kinase 2MiceMice, Inbred C57BLMice, KnockoutNFATC Transcription FactorsAcid PhosphataseAcp5 protein, mouseCathepsin KCtsk protein, mouseIntracellular Signaling Peptides and ProteinsIsoenzymesMAP-Kinase-Activated Kinase 2Nfatc1 protein, mouseNFATC Transcription Factorsp38 Mitogen-Activated Protein KinasesProtein Serine-Threonine KinasesRANK LigandTartrate-Resistant Acid PhosphataseTnfsf11 protein, mouse

Identifiers

PMID25946081
PMCPMC4422514
OpenAlexW249118161

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.