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Wnt Signaling Behaves as a “Master Regulator” in the Osteogenic and Adipogenic Commitment of Human Amniotic Fluid Mesenchymal Stem Cells

Human amniotic fluid mesenchymal stem cells (huAFMSCs) are emerging as a promising therapeutic option in regenerative medicine. Here, we characterized huAFMSC phenotype and multipotentiality. When cultured in osteogenic medium, huAFMSC displayed a significant increase in: Alkaline Phosphatase (ALP)...

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Autores principales: D’Alimonte, Iolanda, Lannutti, Angela, Pipino, Caterina, Di Tomo, Pamela, Pierdomenico, Laura, Cianci, Eleonora, Antonucci, Ivana, Marchisio, Marco, Romano, Mario, Stuppia, Liborio, Caciagli, Francesco, Pandolfi, Assunta, Ciccarelli, Renata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785124/
https://www.ncbi.nlm.nih.gov/pubmed/23605563
http://dx.doi.org/10.1007/s12015-013-9436-5
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author D’Alimonte, Iolanda
Lannutti, Angela
Pipino, Caterina
Di Tomo, Pamela
Pierdomenico, Laura
Cianci, Eleonora
Antonucci, Ivana
Marchisio, Marco
Romano, Mario
Stuppia, Liborio
Caciagli, Francesco
Pandolfi, Assunta
Ciccarelli, Renata
author_facet D’Alimonte, Iolanda
Lannutti, Angela
Pipino, Caterina
Di Tomo, Pamela
Pierdomenico, Laura
Cianci, Eleonora
Antonucci, Ivana
Marchisio, Marco
Romano, Mario
Stuppia, Liborio
Caciagli, Francesco
Pandolfi, Assunta
Ciccarelli, Renata
author_sort D’Alimonte, Iolanda
collection PubMed
description Human amniotic fluid mesenchymal stem cells (huAFMSCs) are emerging as a promising therapeutic option in regenerative medicine. Here, we characterized huAFMSC phenotype and multipotentiality. When cultured in osteogenic medium, huAFMSC displayed a significant increase in: Alkaline Phosphatase (ALP) activity and mRNA expression, Alizarin Red S staining and Runx2 mRNA expression; whereas maintaining these cells in an adipogenic culture medium gave a time-dependent increase in PPARγ and FABP4 mRNA expression, glycerol-3-phosphate dehydrogenase (GPDH) activity and positivity to Oil Red Oil staining. These results confirm that huAFMSCs can differentiate toward osteogenic and adipogenic phenotypes. The canonical Wnt/ßcatenin signaling pathway appears to trigger huAFMSC osteoblastogenesis, since during early phases of osteogenic differentiation, the expression of Dishevelled-2 (Dvl-2), of the non-phosphorylated form of ß-catenin, and the phosphorylation of glycogen synthase kinase-3ß (GSK3ß) at serine 9 were upregulated. On the contrary, during adipogenic differentiation Dvl-2 expression decreased, whereas that of ß-catenin remained unchanged. This was associated with a late increase in GSK3ß phosphorylation. Consistent with this scenario, huAFMSCs exposure to Dickkopf-1, a selective inhibitor of the Wnt signaling, abolished Runx2 and ALP mRNA upregulation during huAFMSC osteogenic differentiation, whereas it enhanced FABP4 expression in adipocyte-differentiating cells. Taken together, these results unravel novel molecular determinants of huAFMSC commitment towards osteoblastogenesis, which may represent potential targets for directing the differentiation of these cells and improving their use in regenerative medicine. [Figure: see text]
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spelling pubmed-37851242013-10-03 Wnt Signaling Behaves as a “Master Regulator” in the Osteogenic and Adipogenic Commitment of Human Amniotic Fluid Mesenchymal Stem Cells D’Alimonte, Iolanda Lannutti, Angela Pipino, Caterina Di Tomo, Pamela Pierdomenico, Laura Cianci, Eleonora Antonucci, Ivana Marchisio, Marco Romano, Mario Stuppia, Liborio Caciagli, Francesco Pandolfi, Assunta Ciccarelli, Renata Stem Cell Rev Article Human amniotic fluid mesenchymal stem cells (huAFMSCs) are emerging as a promising therapeutic option in regenerative medicine. Here, we characterized huAFMSC phenotype and multipotentiality. When cultured in osteogenic medium, huAFMSC displayed a significant increase in: Alkaline Phosphatase (ALP) activity and mRNA expression, Alizarin Red S staining and Runx2 mRNA expression; whereas maintaining these cells in an adipogenic culture medium gave a time-dependent increase in PPARγ and FABP4 mRNA expression, glycerol-3-phosphate dehydrogenase (GPDH) activity and positivity to Oil Red Oil staining. These results confirm that huAFMSCs can differentiate toward osteogenic and adipogenic phenotypes. The canonical Wnt/ßcatenin signaling pathway appears to trigger huAFMSC osteoblastogenesis, since during early phases of osteogenic differentiation, the expression of Dishevelled-2 (Dvl-2), of the non-phosphorylated form of ß-catenin, and the phosphorylation of glycogen synthase kinase-3ß (GSK3ß) at serine 9 were upregulated. On the contrary, during adipogenic differentiation Dvl-2 expression decreased, whereas that of ß-catenin remained unchanged. This was associated with a late increase in GSK3ß phosphorylation. Consistent with this scenario, huAFMSCs exposure to Dickkopf-1, a selective inhibitor of the Wnt signaling, abolished Runx2 and ALP mRNA upregulation during huAFMSC osteogenic differentiation, whereas it enhanced FABP4 expression in adipocyte-differentiating cells. Taken together, these results unravel novel molecular determinants of huAFMSC commitment towards osteoblastogenesis, which may represent potential targets for directing the differentiation of these cells and improving their use in regenerative medicine. [Figure: see text] Springer US 2013-04-19 2013 /pmc/articles/PMC3785124/ /pubmed/23605563 http://dx.doi.org/10.1007/s12015-013-9436-5 Text en © The Author(s) 2013 https://creativecommons.org/licenses/by-nc/2.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Article
D’Alimonte, Iolanda
Lannutti, Angela
Pipino, Caterina
Di Tomo, Pamela
Pierdomenico, Laura
Cianci, Eleonora
Antonucci, Ivana
Marchisio, Marco
Romano, Mario
Stuppia, Liborio
Caciagli, Francesco
Pandolfi, Assunta
Ciccarelli, Renata
Wnt Signaling Behaves as a “Master Regulator” in the Osteogenic and Adipogenic Commitment of Human Amniotic Fluid Mesenchymal Stem Cells
title Wnt Signaling Behaves as a “Master Regulator” in the Osteogenic and Adipogenic Commitment of Human Amniotic Fluid Mesenchymal Stem Cells
title_full Wnt Signaling Behaves as a “Master Regulator” in the Osteogenic and Adipogenic Commitment of Human Amniotic Fluid Mesenchymal Stem Cells
title_fullStr Wnt Signaling Behaves as a “Master Regulator” in the Osteogenic and Adipogenic Commitment of Human Amniotic Fluid Mesenchymal Stem Cells
title_full_unstemmed Wnt Signaling Behaves as a “Master Regulator” in the Osteogenic and Adipogenic Commitment of Human Amniotic Fluid Mesenchymal Stem Cells
title_short Wnt Signaling Behaves as a “Master Regulator” in the Osteogenic and Adipogenic Commitment of Human Amniotic Fluid Mesenchymal Stem Cells
title_sort wnt signaling behaves as a “master regulator” in the osteogenic and adipogenic commitment of human amniotic fluid mesenchymal stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785124/
https://www.ncbi.nlm.nih.gov/pubmed/23605563
http://dx.doi.org/10.1007/s12015-013-9436-5
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