Evidence map›Paper›PMID 20039274›Full record

ArticleJournal of cellular physiology2010

RANKL induces heterogeneous DC-STAMP(lo) and DC-STAMP(hi) osteoclast precursors of which the DC-STAMP(lo) precursors are the master fusogens.

Kofi A Mensah, Christopher T Ritchlin, Edward M Schwarz

Abstract read
In one paragraph

Article in Journal of cellular physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 11% 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

67 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Beyond resorption: osteoclasts as drivers of bone formation.Cell regeneration (London, England) · 2024
    Review
  10. Review
  11. Article
  12. Article
  13. Osteoclasts at Bone Remodeling: Order from Order.Results and problems in cell differentiation · 2024
    Review
  14. Green tea polyphenol EGCg induces cell fusionBiochemistry and biophysics reports · 2023
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

7 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

3 authors at 2 institutions in 1 country.

Kofi A MensahCenter for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York 14642, USA.
Christopher T Ritchlin
Edward M Schwarz
University of Rochester Medical Center · USUniversity of Rochester · US

Funding

UNIVERSITY OF ROCHESTER'S RESEARCH ASSOCIATE ORGANIZATIONUL1RR024160 · NCRR · UNIVERSITY OF ROCHESTER · PI PEARSON, THOMAS ARTHUR · 2006 to 2011
$38.7M
Translating PTH Therapy as an Adjuvant for Structural AllograftingP50AR054041 · NIAMS · UNIVERSITY OF ROCHESTER · PI SCHWARZ, EDWARD M. · 2006 to 2016
$15.7M
University of Rochester Mentoring Environment: Nurturing Training Opportunities in Research (UR-MENTOR)T32GM007356 · NIGMS · UNIVERSITY OF ROCHESTER · PI O'BANION, M. KERRY · 1985 to 2023
$15.1M
Elucidating the Mechanisms of Arthritic Flare and Developing TreatmentsR01AR056702 · NIAMS · UNIVERSITY OF ROCHESTER · PI SCHWARZ, EDWARD M. · 2009 to 2025
$4.9M
The University of Rochester's Clinical and Translational Science InstituteTL1RR024135 · NCRR · UNIVERSITY OF ROCHESTER · PI PEARSON, THOMAS ARTHUR · 2006 to 2011
$3.7M
Prostaglandin Signaling in Wear Debris-induced OsteolysisR01AR046545 · NIAMS · UNIVERSITY OF ROCHESTER · PI O'KEEFE, REGIS J · 2000 to 2009
$3.0M
Testing a Values-Based Approach to Healthcare Decision-Making in Older AdultsF31AG048697 · NIA · UNIVERSITY OF KENTUCKY · PI GEIGER, PAUL J · 2015 to 2016
$86k
NCRR NIH HHS TL1 RR024135NCRR NIH HHS UL1 RR024160NIAMS NIH HHS AR46545NIAMS NIH HHS AR54041NIAMS NIH HHS AR56702NIAMS NIH HHS P50 AR054041NIAMS NIH HHS R01 AR046545NIAMS NIH HHS R01 AR056702NIA NIH HHS AR/AG48697NIA NIH HHS F31 AG048697NIGMS NIH HHS GM07356NIGMS NIH HHS T32 GM007356
6 · The paper itself

Abstract

Osteoclasts (OC) are multinucleated bone resorbing cells that form via RANKL-induced fusion of heterogeneous mononuclear OC precursors (OCP). Currently, there are no unique surface markers to distinguish these OCP populations, which are diagnostic for erosive and metabolic bone diseases using culture assays. Thus, we investigated expression of DC-STAMP, a surface receptor required for OCP fusion, during osteoclastogenesis in vitro using a novel monoclonal antibody (1A2). Immunoprecipitation-Western blot analysis of OCP membrane proteins detected 106 kDa dimeric and 53 kDa monomeric DC-STAMP in non-denaturing and denaturing conditions, respectively, with greater sensitivity versus rabbit anti-sera (KR104). 1A2 also detected 99.9% of undifferentiated monocytes as a single population by flow cytometry with a MFI 100-fold over background, while KR104 was not useful in this assay. Functionally, 1A2 inhibited OCP fusion in vitro. RANKL stimulation of OCP induced DC-STAMP(lo) and DC-STAMP(hi) cells, which mature into OC and mononuclear cells respectively as determined by fluorescent microscopy and TRAP assays. Addition of DC-STAMP(hi) cells to purified DC-STAMP(lo) cultures produced larger, more nucleated OC vs. pure DC-STAMP(lo) cultures. RT-qPCR analysis of these two populations showed that OC markers (Trap and Oc-stamp) and fusogenic gene expression (Cd9 and Cd47), were significantly increased in DC-STAMP(lo) vs. DC-STAMP(hi) cells. Collectively, these results demonstrate that DC-STAMP is expressed on OCP as a dimer, which is efficiently detected by 1A2 via flow cytometry. RANKL induces osteoclastogenesis by stimulating DC-STAMP internalization in some OCP, and these DC-STAMP(lo) cells display the "master fusogen" phenotype. In contrast, DC-STAMP(hi) OCP can only act as mononuclear donors.

Indexed as

Cell DifferentiationCell FusionAcid PhosphataseAnimalsAntigens, CDBiomarkersBlotting, WesternBone Marrow CellsCD47 AntigenCells, CulturedFlow CytometryImmunoproliferative DisordersIsoenzymesMacrophagesMembrane GlycoproteinsMembrane ProteinsAcid PhosphataseAcp5 protein, mouseAntigens, CDBiomarkersCD47 AntigenCd47 protein, mouseCd9 protein, mouseDC-STAMP protein, mouseIsoenzymesMembrane GlycoproteinsMembrane ProteinsNerve Tissue ProteinsOC-STAMP protein, mouseRANK LigandRNA, MessengerTartrate-Resistant Acid PhosphataseTetraspanin 29Cell FusionDendritic Cell-Specific Transmembrane Protein (DC-STAMP)Osteoclast Precursors (OCP)

Identifiers

PMID20039274
PMCPMC2814997
OpenAlexW2168094868

What OpenQuestion holds

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Read underepoch 390

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.