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Molecular and Cellular Biology, March 2005, p. 1971-1979, Vol. 25, No. 5
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.5.1971-1979.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A CCAAT/Enhancer Binding Protein ß Isoform, Liver-Enriched Inhibitory Protein, Regulates Commitment of Osteoblasts and Adipocytes

Kenji Hata,1,2 Riko Nishimura,1* Mio Ueda,1 Fumiyo Ikeda,1 Takuma Matsubara,1 Fumitaka Ichida,1 Kunihiro Hisada,1 Takashi Nokubi,2 Akira Yamaguchi,3 and Toshiyuki Yoneda1

Departments of Biochemistry,1 Removable Prothodontics, Graduate School of Dentistry, Osaka University, Osaka,2 Department of Oral Pathology, Dental School, Graduate School of Medicine, Nagasaki University, Nagasaki, Japan3

Received 16 July 2004/ Returned for modification 9 September 2004/ Accepted 1 December 2004

Although both osteoblasts and adipocytes have a common origin, i.e., mesenchymal cells, the molecular mechanisms that define the direction of two different lineages are presently unknown. In this study, we investigated the role of a transcription factor, CCAAT/enhancer binding protein ß (C/EBPß), and its isoform in the regulation of balance between osteoblast and adipocyte differentiation. We found that C/EBPß, which is induced along with osteoblast differentiation, promotes the differentiation of mesenchymal cells into an osteoblast lineage in cooperation with Runx2, an essential transcription factor for osteogenesis. Surprisingly, an isoform of C/EBPß, liver-enriched inhibitory protein (LIP), which lacks the transcriptional activation domain, stimulates transcriptional activity and the osteogenic action of Runx2, although LIP inhibits adipogenesis in a dominant-negative fashion. Furthermore, LIP physically associates with Runx2 and binds to the C/EBP binding element present in the osteocalcin gene promoter. These data indicate that LIP functions as a coactivator for Runx2 and preferentially promotes the osteoblast differentiation of mesenchymal cells. Thus, identification of a novel role of the C/EBPß isoform provides insight into the molecular basis of the regulation of osteoblast and adipocyte commitment.

* Corresponding author. Mailing address: Department of Biochemistry, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81-6-6879-2887. Fax: 81-6-6879-2890. E-mail: rikonisi{at}dent.osaka-u.ac.jp.

Molecular and Cellular Biology, March 2005, p. 1971-1979, Vol. 25, No. 5
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.5.1971-1979.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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