scholarly journals All-trans retinoic acid shifts rosiglitazone-induced adipogenic differentiation to osteogenic differentiation in mouse embryonic fibroblasts

2016 ◽  
Vol 38 (6) ◽  
pp. 1693-1702 ◽  
Author(s):  
Ying Shao ◽  
Qian-Zhao Chen ◽  
Yu-Hua Zeng ◽  
Yang Li ◽  
Wen-Yan Ren ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Osteogenic Differentiation ◽  
Adipogenic Differentiation ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

scholarly journals E2F1 impairs all-trans retinoic acid-induced osteogenic differentiation of osteosarcoma via promoting ubiquitination-mediated degradation of RARα

Cell Cycle ◽  
2014 ◽  
Vol 13 (8) ◽  
pp. 1277-1287 ◽  
Author(s):  
Lei Zhang ◽  
Qian Zhou ◽  
Ning Zhang ◽  
Weixu Li ◽  
Meidan Ying ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Osteogenic Differentiation ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

scholarly journals All-trans Retinoic Acid Regulates miR-106a-5p Inhibition of Autophagic in Developing Cleft Palates

2020 ◽  
Author(s):  
Lungang Shi ◽  
Yan Liang ◽  
Lijing Yang ◽  
Binchen Li ◽  
Binna Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Retinoic Acid ◽  
Cleft Palate ◽  
Osteogenic Differentiation ◽  
Signaling Pathway ◽  
Differentiation Potential ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Pten Mrna

AbstractBackgroundAll-trans retinoic acid (atRA) results in cleft palate, but the cellular and molecular mechanisms underlying the teratogenic effects on palatal development have not been fully elucidated. Autophagy interruption has been reported to seriously affect embryonic-cell differentiation and development. This study aimed to verify whether atRA-induced cleft palate occurs because atRA blocks autophagy and stemness of embryonic palatal mesenchyme (MEPM) cells, which are maintained via the phosphatase and tensin homolog (PTEN)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) autophagic signaling pathway, and inhibits osteogenic-differentiation potential of MEPM cells, which could lead to the development of cleft palate.MethodsTo assess the stemness and pluripotency of MEPM cells, we analyzed their surfacemarkers using immunofluorescence (IF) and flow cytometry (FCM). Differentiation potentials, such as osteogenic, adipogenic, and chondrogenic differentiation, were induced. We also investigated the role of the PTEN/Akt/mTOR autophagic signaling pathway, which maintains the stemness and pluripotency of MEPM cells. Using transmission electron microscopy (TEM), Western blot analysis, quantitative reverse transcriptase polymerase chain reaction (RT-qPCR), messenger ribonucleic acid (mRNA) microarray, dual-luciferase reporter system, and exosomes, we found that atRA blocks autophagy and osteogenic differentiation of MEPM cells through micro-ribonucleic acid (miR)-106a-5p by targeting the PTEN/Akt/mTOR autophagic pathway.ResultsIn vitro purified MEPM cells expressed cell surface markers similar to those of mouse bone marrow stem cells. Additionally, in vitro MEPM cells were ectomesenchymal and expressed the neural-crest marker human natural killer-1 (HNK-1), the mesodermal marker vimentin, and the ectodermal marker nestin. They were also positive for in vitro MEPM markers, including platelet-derived growth factor alpha (PDGFRα), ephrin B1 (Efnb1), odd-skipped related 2 (Osr2), and Meox2, as well as for stemness markers including POU class 5 homeobox 4 (Oct4), Nanog, and sex-determining region Y-related HMG box 2 (Sox2). MEPM cell pluripotency was retained through activation of the PTEN/Akt/mTOR autophagic signaling pathway. We found that atRA blocked MEPM cell pluripotency to inhibit osteogenic differentiation via miR-106a-5p targeting of PTEN mRNA and subsequent suppression of the PTEN/Akt/mTOR autophagic pathway.ConclusionsIn vitro cultured MEPM cells are ectomesenchymal stem cells that have strong osteogenic differentiation potential, and MEPM pluripotency is regulated by autophagy via the PTEN/AKT/mTOR signaling pathway. atRA disrupts MEPM cell pluripotency through PTEN/AKT/mTOR signaling inactivation where miR-106a-5p targets PTEN mRNA to reduce osteogenic differentiation of MEPM cells and results in the development of cleft palates. Our findings provide new insight into the mechanism underlying the development of cleft palate, and miR-106a-5p may act as a prenatal screening biomarker for cleft palate as well as a new diagnostic and therapeutic target.

scholarly journals All-Trans Retinoic Acid Inhibits Bone Marrow Mesenchymal Stem Cell Commitment to Adipocytes via Upregulating FRA1 Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Linjun Xie ◽  
Liying Zou ◽  
Jie Chen ◽  
Youxue Liu
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Retinoic Acid ◽  
Vitamin A ◽  
Adipogenic Differentiation ◽  
Active Form ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Adipogenic Gene ◽  
Cell Commitment

Obesity, caused by an increased number and volume of adipocytes, is a global epidemic that seriously threatens human health. Bone marrow mesenchymal stem cells (BMSCs) can differentiate into adipocytes. All-trans retinoic acid (atRA, the active form of vitamin A) inhibits the adipogenic differentiation of BMSCs through its receptor RARG. The expression level of FRA1 (FOS like 1, AP-1 transcription factor subunit) in atRA-treated BMSCs increased, suggesting that atRA-mediated inhibition of BMSCs adipogenesis involves FRA1. BMSCs were transfected with adenovirus overexpressing Fra1 (ad-fra1) or silenced for Fra1 (si-fra1) and then treated with atRA. BMSCs treated with atRA and treated with ad-fra1 showed decreased mRNA and protein levels of key adipogenic genes (Pparg2, Cebpa) and adipogenesis-associated genes (Cd36, Fabp, Lpl, and Plin); atRA had a stronger inhibitory effect on adipogenesis compared with that in the ad-fra1 group. Adipogenic gene expression in Fra1-silenced BMSCs was significantly upregulated. Compared with that in the atRA group, the si-fra1 + atRA also upregulated adipogenic gene expression. However, compared with si-fra1, si-fra1 + atRA significantly inhibited adipogenic differentiation. Chromatin immunoprecipitation showed that RARG directly regulates Fra1 and FRA1 directly regulates Pparg2 and Cebpa. The results supported the conclusion that atRA inhibits BMSC adipogenesis partially through the RARG-FRA1-PPARG2 or the CEBPA axis or both. Thus, vitamin A might be used to treat obesity and its related diseases.

All-trans retinoic acid induces mitochondria-mediated apoptosis of human adipose-derived stem cells and affects the balance of the adipogenic differentiation

2017 ◽  
Vol 96 ◽  
pp. 1267-1274 ◽  
Author(s):  
Laynna de Carvalho Schweich ◽  
Edwin José Torres de Oliveira ◽  
João Renato Pesarini ◽  
Larissa Corrêa Hermeto ◽  
Melissa Camassola ◽  
...  
Keyword(s):  
Stem Cells ◽  
Retinoic Acid ◽  
Adipogenic Differentiation ◽  
Adipose Derived Stem Cells ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid
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