Smad3-dependent nuclear translocation of β-catenin is required for TGF-β1-induced proliferation of bone marrow-derived adult human mesenchymal stem cells
- 1 Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA;
- 2 Division of Neuroscience, Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
Abstract
Adult mesenchymal stem cells (MSCs) derived from bone marrow contribute to the regeneration of multiple types of mesenchymal tissues. Here we describe the functional role of a novel form of cross-talk between the transforming growth factor β1 (TGF-β1) and Wnt signaling pathways in regulating the activities of human MSCs. We show that TGF-β1 induces rapid nuclear translocation of β-catenin in MSCs in a Smad3-dependent manner. Functionally, this pathway is required for the stimulation of MSC proliferation and the inhibition of MSC osteogenic differetiation by TGF-β1, likely through the regulation of specific downstream target genes. These results provide evidence for a new mode of cooperation between the TGF-β and Wnt signaling pathways in this specific cellular context and suggest a potentially important role for this distinct signaling pathway in the control of self-renewal and differentiation of a specific type of MSCs.
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Footnotes
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↵3 Corresponding author.
↵3 E-MAIL wang0011{at}mc.duke.edu; FAX (919) 681-7152.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1388806
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- Received October 27, 2005.
- Accepted January 25, 2006.
- Copyright © 2006, Cold Spring Harbor Laboratory Press
