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Cross-talk between Wnt and bone morphogenetic protein (BMP)- 2 signalling in differentiation pathway of C2C12 myoblasts
Title: | Cross-talk between Wnt and bone morphogenetic protein (BMP)- 2 signalling in differentiation pathway of C2C12 myoblasts |
Authors: | Nakashima, Aiko Browse this author | Katagiri, Takanobu Browse this author | Tamura, Masato Browse this author →KAKEN DB |
Keywords: | Wnt | osteoblast | BMP |
Issue Date: | 11-Nov-2005 |
Publisher: | The American Society for Biochemistry and Molecular Biology |
Journal Title: | Journal of Biological Chemistry |
Volume: | 280 |
Issue: | 45 |
Start Page: | 37660 |
End Page: | 37668 |
Publisher DOI: | 10.1074/jbc.M504612200 |
PMID: | 16150699 |
Abstract: | Loss of function of the Wnt co-receptor, lipoprotein receptor-related protein 5, decreases bone formation, and a point mutation in this gene results in high bone mass, indicating the importance of this signalling pathway in bone formation. However, the exact mechanism is currently unknown. We examined a potential role for Wnt signalling and functional cross-talk of bone morphogenetic protein (BMP)-2 in osteoblast differentiation. To assess the contribution of Wnt, we generated C2C12 cells overexpressing Wnt3a or Wnt5a and treated these with BMP-2. We showed that expression of matix extracellular phosphoglycoprotein was induced by BMP-2 in Wnt3a over-expressing C2C12 cells but not in Wnt5a over-expressing C2C12 cells. Overexpression of Wnt3a blocked BMP-2-induced inhibition of myotube formation in C2C12 cells when switched to low mitogen medium. In these cultures, expression of inhibitor of DNA binding/differentiation (Id) 1, a basic helix-loop-helix protein induced by BMP-2, decreased in stable Wnt3a, but not Wnt5a, expressing cells. This suppression is mediated by a GC rich region of the BMP-2 responsive element of the Id1 gene promoter and interaction between Smad1/4 and β-catenin is crucial for Wnt-mediated suppression of the BMP-2 response in C2C12 cells. Overexpression of the inhibitor of canonical Wnt signalling, Dickkopf, inhibits this suppression. In contrast, BMP-2 or Smad1/4 up-regulated Wnt3a or activated β-catenin-induced lymphoid enhancing factor 1/T cell factor-dependent transcriptional activity. These findings identify functional cross-talk of Id1 expression between Wnt and BMP signalling and demonstrate a novel mechanism for Wnt regulation of the BMP-2 response, linking Id1 expression to Wnt/β-catenin signalling. |
Relation: | http://www.jbc.org/ |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/8405 |
Appears in Collections: | 歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 田村 正人
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