Evidence map›Paper›PMID 30203000›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2019

Evidence for Aryl hydrocarbon Receptor-Mediated Inhibition of Osteoblast Differentiation in Human Mesenchymal Stem Cells.

AtLee T D Watson, Rachel C Nordberg, Elizabeth G Loboa, Seth W Kullman

Open access · bronzeAbstract read
In one paragraph

Article in Toxicological sciences : an official journal of the Society of Toxicology, 2019. 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
1.0field-weighted citation impact, top 28% 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, 36 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
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  7. Review
  8. The Role of Aryl Hydrocarbon Receptor in Bone Biology.International journal of tryptophan research : IJTR · 2024
    Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. TCDD alters essential transcriptional regulators of osteogenic differentiation in multipotent mesenchymal stem cells.Toxicological sciences : an official journal of the Society of Toxicology · 2023
    Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Review
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.

AtLee T D WatsonDepartment of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695.
Rachel C NordbergUniversity of North Carolina at Chapel Hill and North Carolina State University Joint Department of Biomedical Engineering, Raleigh, North Carolina 27695 and Chapel Hill, North Carolina 27599.
Elizabeth G LoboaUniversity of North Carolina at Chapel Hill and North Carolina State University Joint Department of Biomedical Engineering, Raleigh, North Carolina 27695 and Chapel Hill, North Carolina 27599.
Seth W KullmanDepartment of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695.
North Carolina State University · USUniversity of North Carolina at Chapel Hill · US

Funding

Zebrafish as a Detector of Organophosphate ExposureP42ES010356 · NIEHS · DUKE UNIVERSITY · PI AMY H HERRING · 2000 to 2026
$56.2M
Translational Research Support CoreP30ES025128 · NIEHS · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI Sue Fenton · 2015 to 2026
$18.3M
TRAINING IN BIOCHEMICAL AND ENVIRONMENTAL TOXICOLOGYT32ES007046 · NIEHS · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI Seth William Kullman · 1985 to 2026
$5.1M
NIEHS NIH HHS P30 ES025128NIEHS NIH HHS P42 ES010356NIEHS NIH HHS T32 ES007046
6 · The paper itself

Abstract

Multipotent mesenchymal stem cells (MSCs) maintain the ability to differentiate into adipogenic, chondrogenic, or osteogenic cell lineages. There is increasing concern that exposure to environmental agents such as aryl hydrocarbon receptor (AhR) ligands, may perturb the osteogenic pathways responsible for normal bone formation. The objective of the current study was to evaluate the potential of the prototypic AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to disrupt osteogenic differentiation of human bone-derived MSCs (hBMSCs) in vitro. Primary hBMSCs from three donors were exposed to 10 nM TCDD and differentiation was interrogated using select histological, biochemical, and transcriptional markers of osteogenesis. Exposure to 10 nM TCDD resulted in an overall consistent attenuation of alkaline phosphatase (ALP) activity and matrix mineralization at terminal stages of differentiation in primary hBMSCs. At the transcriptional level, the transcriptional regulator DLX5 and additional osteogenic markers (ALP, OPN, and IBSP) displayed attenuated expression; conversely, FGF9 and FGF18 were consistently upregulated in each donor. Expression of stem cell potency markers SOX2, NANOG, and SALL4 decreased in the osteogenic controls, whereas expression in TCDD-treated cells resembled that of undifferentiated cells. Coexposure with the AhR antagonist GNF351 blocked TCDD-mediated attenuation of matrix mineralization, and either fully or partially rescued expression of genes associated with osteogenic regulation, extracellular matrix, and/or maintenance of multipotency. Thus, experimental evidence from this study suggests that AhR transactivation likely attenuates osteoblast differentiation in multipotent hBMSCs. This study also underscores the use of primary human MSCs to evaluate osteoinductive or osteotoxic potential of chemical and pharmacologic agents in vitro.

Indexed as

Basic Helix-Loop-Helix ProteinsCell DifferentiationFibroblast Growth Factor 9Fibroblast Growth FactorsHumansLigandsMesenchymal Stem CellsOsteoblastsOsteogenesisPolychlorinated DibenzodioxinsReceptors, Aryl HydrocarbonUp-RegulationAHR protein, humanBasic Helix-Loop-Helix ProteinsFGF9 protein, humanfibroblast growth factor 18Fibroblast Growth Factor 9Fibroblast Growth FactorsLigandsPolychlorinated DibenzodioxinsReceptors, Aryl Hydrocarbon

Identifiers

PMID30203000
PMCPMC6317429
OpenAlexW2892298192

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.