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Cross-talk between Wnt and bone morphogenetic protein (BMP)- 2 signalling in differentiation pathway of C2C12 myoblasts

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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)

Submitter: 田村 正人

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