Evidence map›Paper›PMID 15137062›Full record

ArticleJournal of cellular physiology2004

Roles of stromal cell RANKL, OPG, and M-CSF expression in biphasic TGF-beta regulation of osteoclast differentiation.

Mary Karst, Genevieve Gorny, Rachelle J Sells Galvin, Merry Jo Oursler

Open access · greenAbstract readComparative Study
In one paragraph

Article in Journal of cellular physiology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

89 citing papers in PubMed, 185 citations in OpenAlex.

  1. Review
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  7. The Role of Cytokines in Orthodontic Tooth Movement.International journal of molecular sciences · 2025
    Review
  8. Article
  9. Review
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  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

29 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

4 authors at 2 institutions in 1 country.

Mary KarstDepartment of Biology, University of Minnesota, Duluth, Minnesota, USA.
Genevieve Gorny
Rachelle J Sells Galvin
Merry Jo Oursler
University of Minnesota, Duluth · USEli Lilly (United States) · US

Funding

TGF BETA Regulation of Osteoclast ApoptosisR01DE014680 · NIDCR · UNIVERSITY OF MINNESOTA DULUTH · PI OURSLER, MERRY JO · 2003 to 2007
$1.8M
NIDCR NIH HHS DE14680NIDCR NIH HHS R01 DE014680
6 · The paper itself

Abstract

To better understand the complex roles of transforming growth factor-beta (TGF-beta) in bone metabolism, we examined the impact of a range of TGF-beta concentrations on osteoclast differentiation. In co-cultures of support cells and spleen or marrow osteoclast precursors, low TGF-beta concentrations stimulated while high concentrations inhibited differentiation. We investigated the influences of TGF-beta on macrophage colony stimulating factor (M-CSF), receptor activator of NF-kappaB ligand (RANKL), and osteoprotegerin (OPG) expression and found a dose dependent inhibition of M-CSF expression. RANKL expression was elevated at low TGF-beta concentrations with a less dramatic increase in OPG. Addition of OPG blocked differentiation at the stimulatory TGF-beta dose. Thus, low TGF-beta concentrations elevated the RANKL/OPG ratio while high concentrations did not, supporting that, at low TGF-beta concentrations, there is sufficient M-CSF and a high RANKL/OPG ratio to stimulate differentiation. At high TGF-beta concentrations, the RANKL/OPG ratio and M-CSF expression were both repressed and there was no differentiation. We examined whether TGF-beta-mediated repression of osteoclasts differentiation is due to these changes by adding M-CSF and/or RANKL and did not observe any impact on differentiation repression. We studied direct TGF-beta impacts on osteoclast precursors by culturing spleen or marrow cells with M-CSF and RANKL. TGF-beta treatment dose-dependently stimulated osteoclast differentiation. These data indicate that low TGF-beta levels stimulate osteoclast differentiation by impacting the RANKL/OPG ratio while high TGF-beta levels repress osteoclast differentiation by multiple avenues including mechanisms independent of the RANKL/OPG ratio or M-CSF expression regulation.

Indexed as

Cell DifferentiationAnimalsBone Marrow CellsCarrier ProteinsCells, CulturedCoculture TechniquesDose-Response Relationship, DrugFemaleGene Expression RegulationGlycoproteinsMacrophage Colony-Stimulating FactorMembrane GlycoproteinsMiceMice, Inbred BALB COsteoclastsOsteoprotegerinCarrier ProteinsGlycoproteinsMacrophage Colony-Stimulating FactorMembrane GlycoproteinsOsteoprotegerinRANK LigandReceptor Activator of Nuclear Factor-kappa BReceptors, Cytoplasmic and NuclearReceptors, Tumor Necrosis FactorTgfb1 protein, mouseTnfrsf11a protein, mouseTnfrsf11b protein, mouseTnfsf11 protein, mouseTransforming Growth Factor betaTransforming Growth Factor beta1Transforming Growth Factor beta2

Identifiers

PMID15137062
PMCPMC4547836
OpenAlexW2071619258

What OpenQuestion holds

Textmetadata
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.