Evidence map›Paper›PMID 27562730›Full record

ArticleStem cell research & therapy2016

TGFβ-induced switch from adipogenic to osteogenic differentiation of human mesenchymal stem cells: identification of drug targets for prevention of fat cell differentiation.

Everardus J van Zoelen, Isabel Duarte, José M Hendriks, Sebastian P van der Woning

Abstract read
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Article in Stem cell research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

33 citing papers in PubMed.

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  7. Trichostatin A regulates fibro/adipogenic progenitor adipogenesis epigenetically and reduces rotator cuff muscle fatty infiltration.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2021
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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.

Everardus J van ZoelenDepartment of Cell and Applied Biology, Faculty of Science, Radboud University Nijmegen, PO Box 9010, 6500 GL, Nijmegen, The Netherlands. jovazo@wxs.nl.
Isabel DuarteDepartment of Cell and Applied Biology, Faculty of Science, Radboud University Nijmegen, PO Box 9010, 6500 GL, Nijmegen, The Netherlands.
José M HendriksDepartment of Cell and Applied Biology, Faculty of Science, Radboud University Nijmegen, PO Box 9010, 6500 GL, Nijmegen, The Netherlands.
Sebastian P van der WoningDepartment of Cell and Applied Biology, Faculty of Science, Radboud University Nijmegen, PO Box 9010, 6500 GL, Nijmegen, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPatients suffering from osteoporosis show an increased number of adipocytes in their bone marrow, concomitant with a reduction in the pool of human mesenchymal stem cells (hMSCs) that are able to differentiate into osteoblasts, thus leading to suppressed osteogenesis.

methodsIn order to be able to interfere with this process, we have investigated in-vitro culture conditions whereby adipogenic differentiation of hMSCs is impaired and osteogenic differentiation is promoted. By means of gene expression microarray analysis, we have investigated genes which are potential targets for prevention of fat cell differentiation.

resultsOur data show that BMP2 promotes both adipogenic and osteogenic differentiation of hMSCs, while transforming growth factor beta (TGFβ) inhibits differentiation into both lineages. However, when cells are cultured under adipogenic differentiation conditions, which contain cAMP-enhancing agents such as IBMX of PGE2, TGFβ promotes osteogenic differentiation, while at the same time inhibiting adipogenic differentiation. Gene expression and immunoblot analysis indicated that IBMX-induced suppression of HDAC5 levels plays an important role in the inhibitory effect of TGFβ on osteogenic differentiation. By means of gene expression microarray analysis, we have investigated genes which are downregulated by TGFβ under adipogenic differentiation conditions and may therefore be potential targets for prevention of fat cell differentiation. We thus identified nine genes for which FDA-approved drugs are available. Our results show that drugs directed against the nuclear hormone receptor PPARG, the metalloproteinase ADAMTS5, and the aldo-keto reductase AKR1B10 inhibit adipogenic differentiation in a dose-dependent manner, although in contrast to TGFβ they do not appear to promote osteogenic differentiation.

conclusionsThe approach chosen in this study has resulted in the identification of new targets for inhibition of fat cell differentiation, which may not only be relevant for prevention of osteoporosis, but also of obesity.

Indexed as

AdipocytesAdipogenesisBone MarrowBone Marrow CellsCell DifferentiationCell LineageCells, CulturedDinoprostoneGene ExpressionHistone DeacetylasesHumansMesenchymal Stem CellsOsteoblastsOsteogenesisOsteoporosisTransforming Growth Factor betaDinoprostoneHistone DeacetylasesTransforming Growth Factor betaAdipogenesisAldo-keto reductaseBone marrowHistone deacetylaseMesenchymal stem cellMetalloproteinaseOsteogenesisOsteoporosis

Identifiers

PMID27562730
PMCPMC5000485

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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.