Smad3-dependent nuclear translocation of beta-catenin is required for TGF-beta1-induced proliferation of bone marrow-derived adult human mesenchymal stem cells |
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| Authors: | Jian Hongyan Shen Xing Liu Irwin Semenov Mikhail He Xi Wang Xiao-Fan |
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| Affiliation: | Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA. |
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| 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 beta1 (TGF-beta1) and Wnt signaling pathways in regulating the activities of human MSCs. We show that TGF-beta1 induces rapid nuclear translocation of beta-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 differentiation by TGF-beta1, likely through the regulation of specific downstream target genes. These results provide evidence for a new mode of cooperation between the TGF-beta 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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