Identifying adipogenic chemicals: Disparate effects in 3T3-L1, OP9 and primary mesenchymal multipotent cell models.
Adipogen
Adipogenesis
Multipotent mesenchymal stromal cells
OP9, 3T3-L1
Osteogenesis
PPARγ
RXR
ToxPi
Journal
Toxicology in vitro : an international journal published in association with BIBRA
ISSN: 1879-3177
Titre abrégé: Toxicol In Vitro
Pays: England
ID NLM: 8712158
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
06
02
2020
revised:
18
05
2020
accepted:
22
05
2020
pubmed:
31
5
2020
medline:
13
3
2021
entrez:
31
5
2020
Statut:
ppublish
Résumé
3T3-L1 pre-adipocytes are used commonly to identify new adipogens, but this cell line has been shown to produce variable results. Here, potential adipogenic chemicals (identified in the ToxCast dataset using the Toxicological Priority Index) were tested for their ability to induce adipocyte differentiation in 3T3-L1 cells, OP9 cells and primary mouse bone marrow multipotent stromal cells (BM-MSC). Ten of the 36 potential adipogens stimulated lipid accumulation in at least one model (novel: fenthion, quinoxyfen, prallethrin, allethrin, pyrimethanil, tebuconzaole, 2,4,6-tris (tert-butyl)phenol; known: fentin, pioglitazone, 3,3',5,5'-tetrabromobisphenol A). Only prallethrin and pioglitazone enhanced lipid accumulation in all models. OP9 cells were significantly more sensitive to chemicals known to activate PPARγ through RXR than the other models. Coordinate effects on adipocyte and osteoblast differentiation were investigated further in BM-MSCs. Lipid accumulation was correlated with the ability to stimulate expression of the PPARγ target gene, Plin1. Induction of lipid accumulation also was associated with reduction in alkaline phosphatase activity. Allethrin, prallethrin, and quinoxyfen strongly suppressed osteogenic gene expression. BM-MSCs were useful in coordinately investigating pro-adipogenic and anti-osteogenic effects. Overall, the results show that additional models should be used in conjunction with 3T3-L1 cells to identify a broader spectrum of adipogens and their coordinate effects on osteogenesis.
Identifiants
pubmed: 32473317
pii: S0887-2333(20)30454-9
doi: 10.1016/j.tiv.2020.104904
pmc: PMC9432570
mid: NIHMS1600151
pii:
doi:
Substances chimiques
PPAR gamma
0
PPARG protein, human
0
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
104904Subventions
Organisme : EPA
ID : FP917798
Pays : United States
Organisme : NIEHS NIH HHS
ID : P42 ES007381
Pays : United States
Organisme : NIEHS NIH HHS
ID : R21 ES021136
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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