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首页> 外文期刊>Molecular and Cellular Biology >CCAAT/Enhancer-Binding Protein Homologous Protein (CHOP) Regulates Osteoblast Differentiation
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CCAAT/Enhancer-Binding Protein Homologous Protein (CHOP) Regulates Osteoblast Differentiation

机译：CCAAT /增强子结合蛋白同源蛋白（CHOP）调节成骨细胞分化

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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/EBPζ) 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/EBPβ and inhibits the DNA-binding activity as well as Runx2-binding activity of C/EBPβ, leading to inhibition of osteocalcin gene transcription. These findings indicate that CHOP acts as a dominant-negative inhibitor of C/EBPβ 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.
机译：定型成骨细胞的分化受涉及信号转导和基因表达的复杂活动控制，Runx2和Osterix充当该过程的主要调控因子。最近，据报道，CCAAT /增强子结合蛋白（C / EBPs）除了脂肪形成外，还可以调节成骨作用。但是，C / EBP转录因子在成骨细胞分化控制中的作用尚未完全阐明。在这里，我们显示C / EBP同源蛋白（CHOP;也称为C /EBPζ）在骨骼以及间充质祖细胞和原代成骨细胞中表达。 CHOP的过表达降低了原代成骨细胞中的碱性磷酸酶活性，并抑制了钙化骨结节的形成。缺乏CHOP的成骨细胞比野生型成骨细胞分化更强，表明内源CHOP在抑制成骨细胞分化中起重要作用。此外，内源性CHOP通过骨形态发生蛋白（BMP）处理诱导颅骨成骨细胞分化。 CHOP与C /EBPβ形成异二聚体，并抑制C /EBPβ的DNA结合活性以及Runx2结合活性，从而导致骨钙蛋白基因转录受到抑制。这些发现表明CHOP充当C /EBPβ的显性负抑制剂，并防止成骨细胞分化，但以细胞类型依赖性方式促进BMP信号传导。因此，内源性CHOP可能在调节成骨细胞分化和骨形成中具有双重作用。

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