Canonical Wnts function as potent regulators of osteogenesis by human mesenchymal stem cells
Open Access
- 6 April 2009
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 185 (1), 67-75
- https://doi.org/10.1083/jcb.200810137
Abstract
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.Keywords
This publication has 30 references indexed in Scilit:
- Wnt10b Increases Postnatal Bone Formation by Enhancing Osteoblast DifferentiationJournal of Bone and Mineral Research, 2007
- Cross‐talk between Wnt signaling pathways in human mesenchymal stem cells leads to functional antagonism during osteogenic differentiationJournal of Cellular Biochemistry, 2007
- Canonical WNT Signaling Promotes Osteogenesis by Directly Stimulating Runx2 Gene ExpressionPublished by Elsevier BV ,2005
- How Wnt Signaling Affects Bone Repair by Mesenchymal Stem Cells from the Bone MarrowAnnals of the New York Academy of Sciences, 2005
- Wnt/β-Catenin Signaling in Mesenchymal Progenitors Controls Osteoblast and Chondrocyte Differentiation during Vertebrate SkeletogenesisDevelopmental Cell, 2005
- Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cellsJournal of Cellular Biochemistry, 2004
- Wnt signaling inhibits osteogenic differentiation of human mesenchymal stem cellsBone, 2004
- Control of osteoblast function and regulation of bone massNature, 2003
- High Bone Density Due to a Mutation in LDL-Receptor–Related Protein 5New England Journal of Medicine, 2002
- LDL Receptor-Related Protein 5 (LRP5) Affects Bone Accrual and Eye DevelopmentCell, 2001