2024-03-29T12:29:30Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/84052022-11-17T02:08:08Zhdl_2115_20042hdl_2115_136Cross-talk between Wnt and bone morphogenetic protein (BMP)- 2 signalling in differentiation pathway of C2C12 myoblastsNakashima, AikoKatagiri, TakanobuTamura, MasatoWntosteoblastBMP497Loss 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.The American Society for Biochemistry and Molecular BiologyJournal Articleapplication/pdfhttp://hdl.handle.net/2115/8405https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/8405/1/manuscript.pdf0021-92581083-351XJournal of Biological Chemistry2804537660376682005-11-11enginfo:pmid/16150699info:doi/10.1074/jbc.M504612200author