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Canonical Wnts function as potent regulators of osteogenesis by human mesenchymal stem cells

Genetic evidence indicates that Wnt signaling is critically involved in bone homeostasis. In this study, we investigated the functions of canonical Wnts on differentiation of adult multipotent human mesenchymal stem cells (hMSCs) in vitro and in vivo. We observe differential sensitivities of hMSCs t...

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Autores principales: Liu, Guizhong, Vijayakumar, Sapna, Grumolato, Luca, Arroyave, Randy, Qiao, HuiFang, Akiri, Gal, Aaronson, Stuart A.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2700509/
https://www.ncbi.nlm.nih.gov/pubmed/19349579
http://dx.doi.org/10.1083/jcb.200810137
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author Liu, Guizhong
Vijayakumar, Sapna
Grumolato, Luca
Arroyave, Randy
Qiao, HuiFang
Akiri, Gal
Aaronson, Stuart A.
author_facet Liu, Guizhong
Vijayakumar, Sapna
Grumolato, Luca
Arroyave, Randy
Qiao, HuiFang
Akiri, Gal
Aaronson, Stuart A.
author_sort Liu, Guizhong
collection PubMed
description Genetic evidence indicates that Wnt signaling is critically involved in bone homeostasis. In this study, we investigated the functions of canonical Wnts on differentiation of adult multipotent human mesenchymal stem cells (hMSCs) in vitro and in vivo. We observe differential sensitivities of hMSCs to Wnt inhibition of osteogenesis versus adipogenesis, which favors osteoblastic commitment under binary in vitro differentiation conditions. Wnt inhibition of osteogenesis is associated with decreased expression of osteoblastic transcription factors and inhibition of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activation, which are involved in osteogenic differentiation. An hMSC subpopulation exhibits high endogenous Wnt signaling, the inhibition of which enhances osteogenic and adipogenic differentiation in vitro. In an in vivo bone formation model, high levels of Wnt signaling inhibit de novo bone formation by hMSCs. However, hMSCs with exogenous expression of Wnt1 but not stabilized β-catenin markedly stimulate bone formation by naive hMSCs, arguing for an important role of a canonical Wnt gradient in hMSC osteogenesis in vivo.
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spelling pubmed-27005092009-10-06 Canonical Wnts function as potent regulators of osteogenesis by human mesenchymal stem cells Liu, Guizhong Vijayakumar, Sapna Grumolato, Luca Arroyave, Randy Qiao, HuiFang Akiri, Gal Aaronson, Stuart A. J Cell Biol Research Articles Genetic evidence indicates that Wnt signaling is critically involved in bone homeostasis. In this study, we investigated the functions of canonical Wnts on differentiation of adult multipotent human mesenchymal stem cells (hMSCs) in vitro and in vivo. We observe differential sensitivities of hMSCs to Wnt inhibition of osteogenesis versus adipogenesis, which favors osteoblastic commitment under binary in vitro differentiation conditions. Wnt inhibition of osteogenesis is associated with decreased expression of osteoblastic transcription factors and inhibition of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activation, which are involved in osteogenic differentiation. An hMSC subpopulation exhibits high endogenous Wnt signaling, the inhibition of which enhances osteogenic and adipogenic differentiation in vitro. In an in vivo bone formation model, high levels of Wnt signaling inhibit de novo bone formation by hMSCs. However, hMSCs with exogenous expression of Wnt1 but not stabilized β-catenin markedly stimulate bone formation by naive hMSCs, arguing for an important role of a canonical Wnt gradient in hMSC osteogenesis in vivo. The Rockefeller University Press 2009-04-06 /pmc/articles/PMC2700509/ /pubmed/19349579 http://dx.doi.org/10.1083/jcb.200810137 Text en © 2009 Liu et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Liu, Guizhong
Vijayakumar, Sapna
Grumolato, Luca
Arroyave, Randy
Qiao, HuiFang
Akiri, Gal
Aaronson, Stuart A.
Canonical Wnts function as potent regulators of osteogenesis by human mesenchymal stem cells
title Canonical Wnts function as potent regulators of osteogenesis by human mesenchymal stem cells
title_full Canonical Wnts function as potent regulators of osteogenesis by human mesenchymal stem cells
title_fullStr Canonical Wnts function as potent regulators of osteogenesis by human mesenchymal stem cells
title_full_unstemmed Canonical Wnts function as potent regulators of osteogenesis by human mesenchymal stem cells
title_short Canonical Wnts function as potent regulators of osteogenesis by human mesenchymal stem cells
title_sort canonical wnts function as potent regulators of osteogenesis by human mesenchymal stem cells
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2700509/
https://www.ncbi.nlm.nih.gov/pubmed/19349579
http://dx.doi.org/10.1083/jcb.200810137
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