Publication: EGF Inhibits Wnt/β-Catenin-Induced Osteoblast Differentiation by Promoting β-Catenin Degradation
Issued Date
2015-12-01
Resource Type
ISSN
10974644
07302312
07302312
Other identifier(s)
2-s2.0-84943544563
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Cellular Biochemistry. Vol.116, No.12 (2015), 2849-2857
Suggested Citation
Kanitsak Boonanantanasarn, Hye Lim Lee, Kyunghwa Baek, Kyung Mi Woo, Hyun Mo Ryoo, Jeong Hwa Baek, Gwan Shik Kim EGF Inhibits Wnt/β-Catenin-Induced Osteoblast Differentiation by Promoting β-Catenin Degradation. Journal of Cellular Biochemistry. Vol.116, No.12 (2015), 2849-2857. doi:10.1002/jcb.25231 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/35336
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Title
EGF Inhibits Wnt/β-Catenin-Induced Osteoblast Differentiation by Promoting β-Catenin Degradation
Abstract
© 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc. Bone morphogenetic protein (BMP) and canonical Wnts are representative developmental signals that enhance osteoblast differentiation and bone formation. Previously, we demonstrated that epidermal growth factor (EGF) inhibits BMP2-induced osteoblast differentiation by inducing Smurf1 expression. However, the regulatory role of EGF in Wnt/β-catenin-induced osteoblast differentiation has not been elucidated. In this study, we investigated the effect of EGF on Wnt/β-catenin signaling-induced osteoblast differentiation using the C2C12 cell line. EGF significantly suppressed the expression of osteoblast marker genes, which were induced by Wnt3a and a GSK-3β inhibitor. EGF increased the expression levels of Smurf1 mRNA and protein. Smurf1 knockdown rescued Wnt/β-catenin-induced osteogenic marker gene expression in the presence of EGF. EGF treatment or Smurf1 overexpression did not affect β-catenin mRNA expression levels, but reduced β-catenin protein levels and TOP-Flash activity. EGF and Smurf1 promoted β-catenin ubiquitination. Co-immunoprecipitation and GST pull-down assays showed that Smurf1 associates with β-catenin. These results suggest that EGF/Smurf1 inhibits Wnt/β-catenin-induced osteogenic differentiation and that Smurf1 downregulates Wnt/β-catenin signaling by enhancing proteasomal degradation of β-catenin. J. Cell. Biochem. 116: 2849-2857, 2015.