Evidence map›Paper›PMID 23598406›Full record

ArticleCell death & disease2013

Low FasL levels promote proliferation of human bone marrow-derived mesenchymal stem cells, higher levels inhibit their differentiation into adipocytes.

M R Rippo, L Babini, F Prattichizzo, L Graciotti, G Fulgenzi, F Tomassoni Ardori, F Olivieri, G Borghetti, S Cinti, A Poloni and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed, 27 citations in OpenAlex.

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  11. FasL Modulates Expression ofFrontiers in physiology · 2018
    Article
  12. Article
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  15. TNF-related apoptosis-inducing ligand promotes human preadipocyte proliferation via ERK1/2 activation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015
    Article
  16. Article
  17. 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

12 authors at 4 institutions in 2 countries.

M R RippoLaboratory of Experimental Pathology, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy. m.r.rippo@univpm.it
L Babini
F Prattichizzo
L Graciotti
G Fulgenzi
F Tomassoni Ardori
F Olivieri
G Borghetti
S Cinti
A Poloni
F Fazioli
A D Procopio
Marche Polytechnic University · ITCancer Genetics (United States) · USIstituto Nazionale di Riposo e Cura per Anziani · ITNational Cancer Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mesenchymal stem cells (MSCs) are multipotent progenitor cells that can differentiate into several cell types. Bone marrow (BM)-MSCs mainly differentiate into osteoblasts or adipocytes. MSC interactions with their microenvironment directly affect their self-renewal/differentiation program. Here, we show for the first time that Fas ligand (FasL), a well-explored proapoptotic cytokine, can promote proliferation of BM-derived MSCs in vitro and inhibits their differentiation into adipocytes. BM-MSCs treated with a low FasL dose (0.5 ng/ml) proliferated more rapidly than untreated cells without undergoing spontaneous differentiation or apoptosis, whereas higher doses (25 ng/ml) induced significant though not massive BM-MSC death, with surviving cells maintaining a stem cell phenotype. At the molecular level, 0.5 ng/ml FasL induced ERK1/2 phosphorylation and survivin upregulation, whereas 25 ng/ml FasL induced caspase activation. Importantly, 25 ng/ml FasL reversibly prevented BM-MSC differentiation into adipocytes by modulating peroxisome proliferator-activated receptor gamma (PPARγ) and FABP4/aP2 expression induced by adipogenic medium. All such effects were inhibited by anti-Fas neutralizing antibody. The in vitro data regarding adipogenesis were confirmed using Fas(lpr) mutant mice, where higher PPARγ and FABP4/aP2 mRNA and protein levels were documented in whole tibia. These data show for the first time that the FasL/Fas system can have a role in BM-MSC biology via regulation of both proliferation and adipogenesis, and may have clinical relevance because circulating Fas/FasL levels decline with age and several age-related conditions, including osteoporosis, are characterized by adipocyte accumulation in BM.

Indexed as

AdipogenesisAnimalsAntibodies, NeutralizingBone Marrow CellsCaspasesCell ProliferationCells, CulturedFas Ligand ProteinFatty Acid-Binding ProteinsHumansInhibitor of Apoptosis ProteinsMesenchymal Stem CellsMiceMice, Inbred C57BLMice, TransgenicMitogen-Activated Protein Kinase 1Antibodies, NeutralizingBIRC5 protein, humanCaspasesFABP4 protein, humanFas Ligand ProteinFatty Acid-Binding ProteinsInhibitor of Apoptosis ProteinsMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3PPAR gammaRecombinant ProteinsSurvivin

Identifiers

PMID23598406
PMCPMC3641338
OpenAlexW1994902609

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.