This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shirakawa, K.
Right arrow Articles by Imamura, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shirakawa, K.
Right arrow Articles by Imamura, T.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2006, p. 6105-6116, Vol. 26, No. 16
0270-7306/06/$08.00+0     doi:10.1128/MCB.02429-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

CCAAT/Enhancer-Binding Protein Homologous Protein (CHOP) Regulates Osteoblast Differentiation

Ken Shirakawa,1,2,{dagger} Shingo Maeda,1,{dagger} Tomomi Gotoh,3 Makoto Hayashi,1,4 Kenichi Shinomiya,2 Shogo Ehata,1 Riko Nishimura,5 Masataka Mori,3 Kikuo Onozaki,6 Hidetoshi Hayashi,6 Satoshi Uematsu,7 Shizuo Akira,7 Etsuro Ogata,8 Kohei Miyazono,1,9 and Takeshi Imamura1*

Department of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo,1 Section of Orthopedic and Spinal Surgery, Department of Frontier Surgical Therapeutics, Division of Advanced Therapeutical Sciences, Graduate School, Tokyo Medical and Dental University, Tokyo,2 Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto,3 Department of Biological Sciences, Graduate School of Bioscienceand Biotechnology, Tokyo Institute of Technology, Yokohama,4 Department of Biochemistry, Graduate School of Dentistry, Osaka University, Osaka,5 Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya,6 Exploratory Research for Advanced Technology, Japan Science and Technology Agency, Department of Host Defense, and The 21st Century COE, Combined Program on Microbiology and Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka,7 Cancer Institute Hospital, Tokyo,8 Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan9

Received 21 December 2005/ Returned for modification 20 February 2006/ Accepted 26 May 2006

Differentiation of committed osteoblasts is controlled by complex activities involving signal transduction and gene expression, and Runx2 and Osterix function as master regulators for this process. Recently, CCAAT/enhancer-binding proteins (C/EBPs) have been reported to regulate osteogenesis in addition to adipogenesis. However, the roles of C/EBP transcription factors in the control of osteoblast differentiation have yet to be fully elucidated. Here we show that C/EBP homologous protein (CHOP; also known as C/EBP{zeta}) is expressed in bone as well as in mesenchymal progenitors and primary osteoblasts. Overexpression of CHOP reduces alkaline phosphatase activity in primary osteoblasts and suppresses the formation of calcified bone nodules. CHOP-deficient osteoblasts differentiate more strongly than their wild-type counterparts, suggesting that endogenous CHOP plays an important role in the inhibition of osteoblast differentiation. Furthermore, endogenous CHOP induces differentiation of calvarial osteoblasts upon bone morphogenetic protein (BMP) treatment. CHOP forms heterodimers with C/EBPß and inhibits the DNA-binding activity as well as Runx2-binding activity of C/EBPß, leading to inhibition of osteocalcin gene transcription. These findings indicate that CHOP acts as a dominant-negative inhibitor of C/EBPß and prevents osteoblast differentiation but promotes BMP signaling in a cell-type-dependent manner. Thus, endogenous CHOP may have dual roles in regulating osteoblast differentiation and bone formation.

* Corresponding author. Mailing address: Department of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), 3-10-6, Ariake, Koto-ku, Tokyo 135-8550, Japan. Phone: 81-3-3570-0459. Fax: 81-3-3570-0459. E-mail: timamura-ind{at}umin.ac.jp.

{dagger} These authors contributed equally.

Molecular and Cellular Biology, August 2006, p. 6105-6116, Vol. 26, No. 16
0270-7306/06/$08.00+0     doi:10.1128/MCB.02429-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zhang, Y., Larade, K., Jiang, Z.-g., Ito, S., Wang, W., Zhu, H., Bunn, H. F. (2010). The flavoheme reductase Ncb5or protects cells against endoplasmic reticulum stress-induced lipotoxicity. J. Lipid Res. 51: 53-62 [Abstract] [Full Text]  
  • Zanotti, S., Stadmeyer, L., Smerdel-Ramoya, A., Durant, D., Canalis, E. (2009). Misexpression of CCAAT/enhancer binding protein beta causes osteopenia. J Endocrinol 201: 263-274 [Abstract] [Full Text]  
  • Tominaga, H., Maeda, S., Hayashi, M., Takeda, S., Akira, S., Komiya, S., Nakamura, T., Akiyama, H., Imamura, T. (2008). CCAAT/Enhancer-binding Protein {beta} Promotes Osteoblast Differentiation by Enhancing Runx2 Activity with ATF4. Mol. Biol. Cell 19: 5373-5386 [Abstract] [Full Text]  
  • Cucinotta, M., Visalli, M., Aguennouz, M., Valenti, A., Loddo, S., Altucci, L., Teti, D. (2008). Regulation of Interleukin-8 Gene at a Distinct Site of Its Promoter by CCAAT Enhancer-binding Protein Homologous Protein in Prostaglandin E2-treated Human T Cells. J. Biol. Chem. 283: 29760-29769 [Abstract] [Full Text]  
  • Yamakawa, T., Whitson, R. H., Li, S.-L., Itakura, K. (2008). Modulator Recognition Factor-2 Is Required for Adipogenesis in Mouse Embryo Fibroblasts and 3T3-L1 Cells. Mol. Endocrinol. 22: 441-453 [Abstract] [Full Text]  
  • Hayashi, M., Maeda, S., Aburatani, H., Kitamura, K., Miyoshi, H., Miyazono, K., Imamura, T. (2008). Pitx2 Prevents Osteoblastic Transdifferentiation of Myoblasts by Bone Morphogenetic Proteins. J. Biol. Chem. 283: 565-571 [Abstract] [Full Text]  
  • Wiper-Bergeron, N., St-Louis, C., Lee, J. M. (2007). CCAAT/Enhancer Binding Protein {beta} Abrogates Retinoic Acid-Induced Osteoblast Differentiation via Repression of Runx2 Transcription. Mol. Endocrinol. 21: 2124-2135 [Abstract] [Full Text]  
  • Lawrence, M. C., McGlynn, K., Naziruddin, B., Levy, M. F., Cobb, M. H. (2007). Inaugural Article: Differential regulation of CHOP-10/GADD153 gene expression by MAPK signaling in pancreatic beta-cells. Proc. Natl. Acad. Sci. USA 104: 11518-11525 [Abstract] [Full Text]  
  • Mameli, G., Deshmane, S. L., Ghafouri, M., Cui, J., Simbiri, K., Khalili, K., Mukerjee, R., Dolei, A., Amini, S., Sawaya, B. E. (2007). C/EBPbeta regulates human immunodeficiency virus 1 gene expression through its association with cdk9. J. Gen. Virol. 88: 631-640 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»