scholarly journals Loss-of-Function of HtrA1 Abrogates All-Trans Retinoic Acid-Induced Osteogenic Differentiation of Mouse Adipose-Derived Stromal Cells Through Deficiencies in p70S6K Activation

2016 ◽  
Vol 25 (9) ◽  
pp. 687-698 ◽  
Author(s):  
Stephan Glanz ◽  
Ali Mirsaidi ◽  
Cristina López-Fagundo ◽  
Gladys Filliat ◽  
André N. Tiaden ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Osteogenic Differentiation ◽  
Stromal Cells ◽  
Loss Of Function ◽  
Trans Retinoic Acid ◽  
Adipose Derived Stromal Cells ◽  
All Trans Retinoic Acid ◽  
P70s6k Activation

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 How to overcome the ATRA resistance with the 9aaTAD activation domains in retinoic acid receptors

2018 ◽  
Author(s):  
Martin Piskacek ◽  
Marek Havelka ◽  
Andrea Knight
Keyword(s):  
Retinoic Acid ◽  
Hormone Receptors ◽  
Activation Function ◽  
Receptor Activation ◽  
Nuclear Hormone Receptor ◽  
Nuclear Hormone Receptors ◽  
Loss Of Function ◽  
Activation Domains ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

AbstractIn higher metazoa, the nuclear hormone receptors activate transcription trough their specific adaptors, nuclear hormone receptor cofactors NCoA, which are surprisingly absent in lower metazoa. In this study, we demonstrated that the 9aaTAD from NHR-49 receptor activates transcription as a small peptide. We showed, that the 9aaTAD domains are conserved in the human nuclear hormone receptors including HNF4, RARa, VDR and PPARg. The small 9aaTAD peptides derived from these nuclear hormone receptors also effectively activated transcription and that in absence of the NCoA adaptors. We identified adjacent inhibitory domains in the human HNF4 and RARa, which hindered their activation function.In acute promyelocytic leukaemia (PML-RARa), the receptor mutations often caused all-trans retinoic acid (ATRA) resistance. The fact that almost the entire receptor is needed for ATRA mediated receptor activation, this activation pathway is highly susceptible for loss of function when mutated. Nevertheless in the most of the reported mutants, the activation domains 9aaTAD are still intact. The release of activation 9aaTAD from its dormancy by a new drug might be the sound strategy in combat the ATRA resistance in PML leukaemia.Graphical Abstract

All-trans retinoic acid directly up-regulates thrombopoietin transcription in human bone marrow stromal cells

2004 ◽  
Vol 32 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Kentaro Kinjo ◽  
Yoshitaka Miyakawa ◽  
Hideo Uchida ◽  
Shigetaka Kitajima ◽  
Yasuo Ikeda ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Retinoic Acid ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid
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