A CCAAT/enhancer binding protein β isoform, liver-enriched inhibitory protein, regulates commitment of osteoblasts and adipocytes

Kenji Hata, Riko Nishimura, Mio Ueda, Fumiyo Ikeda, Takuma Matsubara, Fumitaka Ichida, Kunihiro Hisada, Takashi Nokubi, Akira Yamaguchi, Toshiyuki Yoneda

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

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 β (C/EBPβ), and its isoform in the regulation of balance between osteoblast and adipocyte differentiation. We found that C/EBPβ, 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/EBPβ, 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/EBPβ isoform provides insight into the molecular basis of the regulation of osteoblast and adipocyte commitment.

Original languageEnglish
Pages (from-to)1971-1979
Number of pages9
JournalMolecular and cellular biology
Volume25
Issue number5
DOIs
Publication statusPublished - Mar 2005

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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