Inhibition of hedgehog signaling decreases proliferation and clonogenicity of human mesenchymal stem cells.

Human mesenchymal stem cells (hMSC) have the ability to differentiate into osteoblasts, adipocytes and chondrocytes. We have previously shown that hMSC were endowed with a basal level of Hedgehog signaling that decreased after differentiation of these cells. Since hMSC differentiation is associated...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Magali Plaisant, Sophie Giorgetti-Peraldi, Marike Gabrielson, Agnes Loubat, Christian Dani, Pascal Peraldi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b3f91662e1404d1a88c2f4da9e6dea70
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b3f91662e1404d1a88c2f4da9e6dea70
record_format	dspace
spelling	oai:doaj.org-article:b3f91662e1404d1a88c2f4da9e6dea702021-11-18T06:59:16ZInhibition of hedgehog signaling decreases proliferation and clonogenicity of human mesenchymal stem cells.1932-620310.1371/journal.pone.0016798https://doaj.org/article/b3f91662e1404d1a88c2f4da9e6dea702011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21304817/?tool=EBIhttps://doaj.org/toc/1932-6203Human mesenchymal stem cells (hMSC) have the ability to differentiate into osteoblasts, adipocytes and chondrocytes. We have previously shown that hMSC were endowed with a basal level of Hedgehog signaling that decreased after differentiation of these cells. Since hMSC differentiation is associated with growth-arrest we investigated the function of Hh signaling on cell proliferation. Here, we show that inhibition of Hh signaling, using the classical inhibitor cyclopamine, or a siRNA directed against Gli-2, leads to a decrease in hMSC proliferation. This phenomenon is not linked to apoptosis but to a block of the cells in the G0/G1 phases of the cell cycle. At the molecular level, it is associated with an increase in the active form of pRB, and a decrease in cyclin A expression and MAP kinase phosphorylation. Inhibition of Hh signaling is also associated with a decrease in the ability of the cells to form clones. By contrast, inhibition of Hh signaling during hMSC proliferation does not affect their ability to differentiate. This study demonstrates that hMSC are endowed with a basal Hedgehog signaling activity that is necessary for efficient proliferation and clonogenicity of hMSC. This observation unravels an unexpected new function for Hedgehog signaling in the regulation of human mesenchymal stem cells and highlights the critical function of this morphogen in hMSC biology.Magali PlaisantSophie Giorgetti-PeraldiMarike GabrielsonAgnes LoubatChristian DaniPascal PeraldiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 2, p e16798 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Magali Plaisant Sophie Giorgetti-Peraldi Marike Gabrielson Agnes Loubat Christian Dani Pascal Peraldi Inhibition of hedgehog signaling decreases proliferation and clonogenicity of human mesenchymal stem cells.
description	Human mesenchymal stem cells (hMSC) have the ability to differentiate into osteoblasts, adipocytes and chondrocytes. We have previously shown that hMSC were endowed with a basal level of Hedgehog signaling that decreased after differentiation of these cells. Since hMSC differentiation is associated with growth-arrest we investigated the function of Hh signaling on cell proliferation. Here, we show that inhibition of Hh signaling, using the classical inhibitor cyclopamine, or a siRNA directed against Gli-2, leads to a decrease in hMSC proliferation. This phenomenon is not linked to apoptosis but to a block of the cells in the G0/G1 phases of the cell cycle. At the molecular level, it is associated with an increase in the active form of pRB, and a decrease in cyclin A expression and MAP kinase phosphorylation. Inhibition of Hh signaling is also associated with a decrease in the ability of the cells to form clones. By contrast, inhibition of Hh signaling during hMSC proliferation does not affect their ability to differentiate. This study demonstrates that hMSC are endowed with a basal Hedgehog signaling activity that is necessary for efficient proliferation and clonogenicity of hMSC. This observation unravels an unexpected new function for Hedgehog signaling in the regulation of human mesenchymal stem cells and highlights the critical function of this morphogen in hMSC biology.
format	article
author	Magali Plaisant Sophie Giorgetti-Peraldi Marike Gabrielson Agnes Loubat Christian Dani Pascal Peraldi
author_facet	Magali Plaisant Sophie Giorgetti-Peraldi Marike Gabrielson Agnes Loubat Christian Dani Pascal Peraldi
author_sort	Magali Plaisant
title	Inhibition of hedgehog signaling decreases proliferation and clonogenicity of human mesenchymal stem cells.
title_short	Inhibition of hedgehog signaling decreases proliferation and clonogenicity of human mesenchymal stem cells.
title_full	Inhibition of hedgehog signaling decreases proliferation and clonogenicity of human mesenchymal stem cells.
title_fullStr	Inhibition of hedgehog signaling decreases proliferation and clonogenicity of human mesenchymal stem cells.
title_full_unstemmed	Inhibition of hedgehog signaling decreases proliferation and clonogenicity of human mesenchymal stem cells.
title_sort	inhibition of hedgehog signaling decreases proliferation and clonogenicity of human mesenchymal stem cells.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/b3f91662e1404d1a88c2f4da9e6dea70
work_keys_str_mv	AT magaliplaisant inhibitionofhedgehogsignalingdecreasesproliferationandclonogenicityofhumanmesenchymalstemcells AT sophiegiorgettiperaldi inhibitionofhedgehogsignalingdecreasesproliferationandclonogenicityofhumanmesenchymalstemcells AT marikegabrielson inhibitionofhedgehogsignalingdecreasesproliferationandclonogenicityofhumanmesenchymalstemcells AT agnesloubat inhibitionofhedgehogsignalingdecreasesproliferationandclonogenicityofhumanmesenchymalstemcells AT christiandani inhibitionofhedgehogsignalingdecreasesproliferationandclonogenicityofhumanmesenchymalstemcells AT pascalperaldi inhibitionofhedgehogsignalingdecreasesproliferationandclonogenicityofhumanmesenchymalstemcells
_version_	1718424127353651200

Inhibition of hedgehog signaling decreases proliferation and clonogenicity of human mesenchymal stem cells.

Ejemplares similares