A CCAAT/enhancer binding protein β isoform, liver-enriched inhibitory protein, regulates commitment of osteoblasts and adipocytes
A CCAAT/enhancer binding protein β isoform, liver-enriched inhibitory protein, regulates commitment of osteoblasts and adipocytes
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DOI：
10.1128/mcb.25.5.1971-1979.2005
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发表时间：
2005-03-01
影响因子：
5.3
通讯作者：
Yoneda, T
中科院分区：
文献类型：
--
作者：
Hata, K;Nishimura, R;Yoneda, T
虽然成骨细胞和脂肪细胞具有共同的起源，即，虽然两种细胞系都是间充质细胞，但定义两种不同谱系方向的分子机制目前尚不清楚。在这项研究中，我们研究了转录因子CCAAT/增强子结合蛋白β（C/EBP β）及其亚型在成骨细胞和脂肪细胞分化平衡调节中的作用。我们发现，C/EBP β，这是诱导沿着成骨细胞分化，促进间充质细胞分化成成骨细胞谱系与Runx 2，一个必要的转录因子成骨。令人惊讶的是，C/EBP β的同种型，肝脏富集的抑制蛋白（LIP），缺乏转录激活结构域，刺激Runx 2的转录活性和成骨作用，尽管LIP以显性负性方式抑制脂肪形成。此外，LIP与Runx 2物理结合并结合骨钙素基因启动子中存在的C/EBP结合元件。这些数据表明，LIP作为Runx 2的共激活因子发挥作用，并优先促进间充质细胞的成骨细胞分化。因此，鉴定C/EBP β亚型的新作用，提供了对成骨细胞和脂肪细胞定向调控的分子基础的深入了解。
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 beta (C/EBPbeta), and its isoform in the regulation of balance between osteoblast and adipocyte differentiation. We found that C/EBPbeta, which is induced along with osteoblast differentiation, promotes the differentiation of mesenchymall cells into an osteoblast lineage in cooperation with Runx2, an essential transcription factor for osteogenesis. Surprisingly, an isoform of C/EBPbeta, 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 mesenchymall cells. Thus, identification of a novel role of the C/EBPbeta isoform, provides insight into the molecular basis of the regulation of osteoblast and adipocyte commitment.