Cargando…

Transforming Growth Factor-β1 (TGF-β1) Induces Mouse Precartilaginous Stem Cell Proliferation through TGF-β Receptor II (TGFRII)-Akt-β-Catenin Signaling

Precartilaginous stem cells (PSCs) could self-renew or differentiate into chondrocytes to promote bone growth. In the current study, we aim to understand the role of transforming growth factor-β1 (TGF-β1) in precartilaginous stem cell (PSC) proliferation, and to study the underlying mechanisms. We s...

Descripción completa

Detalles Bibliográficos
Autores principales: Cheng, Li, Zhang, Chengyu, Li, Ding, Zou, Jian, Wang, Junfang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139866/
https://www.ncbi.nlm.nih.gov/pubmed/25036031
http://dx.doi.org/10.3390/ijms150712665
_version_ 1782331429466669056
author Cheng, Li
Zhang, Chengyu
Li, Ding
Zou, Jian
Wang, Junfang
author_facet Cheng, Li
Zhang, Chengyu
Li, Ding
Zou, Jian
Wang, Junfang
author_sort Cheng, Li
collection PubMed
description Precartilaginous stem cells (PSCs) could self-renew or differentiate into chondrocytes to promote bone growth. In the current study, we aim to understand the role of transforming growth factor-β1 (TGF-β1) in precartilaginous stem cell (PSC) proliferation, and to study the underlying mechanisms. We successfully purified and primary-cultured PSCs from the neonate mice’ perichondrial mesenchyme, and their phenotype was confirmed by the PSC marker fibroblast growth factor receptor-3 (FGFR-3) overexpression. We found that TGF-β1 induced Akt-glycogen synthase kinase-3β (GSK3β) phosphorylation and β-catenin nuclear translocation in the mouse PSCs, which was almost blocked by TGF-β receptor-II (TGFRII) shRNA knockdown. Further, perifosine and MK-2206, two Akt-specific inhibitors, suppressed TGF-β1-induced GSK3β phosphorylation and β-catenin nuclear translocation. Akt inhibitors, as well as β-catenin shRNA knockdown largely inhibited TGF-β1-stimulated cyclin D1/c-myc gene transcription and mouse PSC proliferation. Based on these results, we suggest that TGF-β1 induces Akt activation to promote β-catenin nuclear accumulation, which then regulates cyclin D1/c-myc gene transcription to eventually promote mouse PSC proliferation.
format Online
Article
Text
id pubmed-4139866
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-41398662014-08-21 Transforming Growth Factor-β1 (TGF-β1) Induces Mouse Precartilaginous Stem Cell Proliferation through TGF-β Receptor II (TGFRII)-Akt-β-Catenin Signaling Cheng, Li Zhang, Chengyu Li, Ding Zou, Jian Wang, Junfang Int J Mol Sci Article Precartilaginous stem cells (PSCs) could self-renew or differentiate into chondrocytes to promote bone growth. In the current study, we aim to understand the role of transforming growth factor-β1 (TGF-β1) in precartilaginous stem cell (PSC) proliferation, and to study the underlying mechanisms. We successfully purified and primary-cultured PSCs from the neonate mice’ perichondrial mesenchyme, and their phenotype was confirmed by the PSC marker fibroblast growth factor receptor-3 (FGFR-3) overexpression. We found that TGF-β1 induced Akt-glycogen synthase kinase-3β (GSK3β) phosphorylation and β-catenin nuclear translocation in the mouse PSCs, which was almost blocked by TGF-β receptor-II (TGFRII) shRNA knockdown. Further, perifosine and MK-2206, two Akt-specific inhibitors, suppressed TGF-β1-induced GSK3β phosphorylation and β-catenin nuclear translocation. Akt inhibitors, as well as β-catenin shRNA knockdown largely inhibited TGF-β1-stimulated cyclin D1/c-myc gene transcription and mouse PSC proliferation. Based on these results, we suggest that TGF-β1 induces Akt activation to promote β-catenin nuclear accumulation, which then regulates cyclin D1/c-myc gene transcription to eventually promote mouse PSC proliferation. MDPI 2014-07-17 /pmc/articles/PMC4139866/ /pubmed/25036031 http://dx.doi.org/10.3390/ijms150712665 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Cheng, Li
Zhang, Chengyu
Li, Ding
Zou, Jian
Wang, Junfang
Transforming Growth Factor-β1 (TGF-β1) Induces Mouse Precartilaginous Stem Cell Proliferation through TGF-β Receptor II (TGFRII)-Akt-β-Catenin Signaling
title Transforming Growth Factor-β1 (TGF-β1) Induces Mouse Precartilaginous Stem Cell Proliferation through TGF-β Receptor II (TGFRII)-Akt-β-Catenin Signaling
title_full Transforming Growth Factor-β1 (TGF-β1) Induces Mouse Precartilaginous Stem Cell Proliferation through TGF-β Receptor II (TGFRII)-Akt-β-Catenin Signaling
title_fullStr Transforming Growth Factor-β1 (TGF-β1) Induces Mouse Precartilaginous Stem Cell Proliferation through TGF-β Receptor II (TGFRII)-Akt-β-Catenin Signaling
title_full_unstemmed Transforming Growth Factor-β1 (TGF-β1) Induces Mouse Precartilaginous Stem Cell Proliferation through TGF-β Receptor II (TGFRII)-Akt-β-Catenin Signaling
title_short Transforming Growth Factor-β1 (TGF-β1) Induces Mouse Precartilaginous Stem Cell Proliferation through TGF-β Receptor II (TGFRII)-Akt-β-Catenin Signaling
title_sort transforming growth factor-β1 (tgf-β1) induces mouse precartilaginous stem cell proliferation through tgf-β receptor ii (tgfrii)-akt-β-catenin signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139866/
https://www.ncbi.nlm.nih.gov/pubmed/25036031
http://dx.doi.org/10.3390/ijms150712665
work_keys_str_mv AT chengli transforminggrowthfactorb1tgfb1inducesmouseprecartilaginousstemcellproliferationthroughtgfbreceptoriitgfriiaktbcateninsignaling
AT zhangchengyu transforminggrowthfactorb1tgfb1inducesmouseprecartilaginousstemcellproliferationthroughtgfbreceptoriitgfriiaktbcateninsignaling
AT liding transforminggrowthfactorb1tgfb1inducesmouseprecartilaginousstemcellproliferationthroughtgfbreceptoriitgfriiaktbcateninsignaling
AT zoujian transforminggrowthfactorb1tgfb1inducesmouseprecartilaginousstemcellproliferationthroughtgfbreceptoriitgfriiaktbcateninsignaling
AT wangjunfang transforminggrowthfactorb1tgfb1inducesmouseprecartilaginousstemcellproliferationthroughtgfbreceptoriitgfriiaktbcateninsignaling