The cartilage‐specific transcription factor Sox9 regulates AP‐2ε expression in chondrocytes

The cartilage‐specific transcription factor Sox9 regulates AP‐2ε expression in chondrocytes
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软骨特异性转录因子 Sox9 调节软骨细胞中 AP-2ε 的表达

DOI:
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发表时间:
2009
期刊:
The FEBS Journal
影响因子:
--
通讯作者:
A. Bosserhoff
A. Bosserhoff
中科院分区:
--
文献类型:
--
作者:
Ann;S. Grässel;M. Moser;A. Bosserhoff

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激活增强子结合蛋白(AP) - 2ε先前被描述为软骨中整合素α10表达的新调节剂。在这项研究中,我们分析了AP‐2ε在分化软骨细胞和人间充质干细胞(HMSCs)中的表达,这些细胞已经在体外分化为软骨细胞。AP‐2ε主要在软骨细胞分化的晚期表达,主要是在早期肥大的软骨中,这与小鼠胚胎切片的免疫组织化学染色一致。此外,骨关节炎软骨细胞,类似于肥厚表型,具有高AP‐2ε水平。AP‐2ε启动子包含转录因子AP‐2α和Sox9的结合位点。在软骨肉瘤细胞系SW1353中,这两种转录因子以合作的方式强烈激活AP‐2ε表达。小干扰RNA抑制Sox9表达导致AP‐2ε表达降低。此外,Sox9与AP‐2ε启动子的直接相互作用可以通过染色质免疫沉淀和电迁移转移实验得到证实。这是第一个证明转录因子Sox9直接调控AP‐2ε的研究,并表明AP‐2ε可能作为增生性软骨的调节剂发挥重要作用。
Activating enhancer‐binding protein (AP)‐2ε was previously described as a new regulator of integrin α10 expression in cartilage. In this study, we analyzed the expression of AP‐2ε in differentiated chondrocytes and in human mesenchymal stem cells (HMSCs), which have been differentiated into chondrocytes in vitro. AP‐2ε is predominantly expressed during the late stages of chondrocyte differentiation, mainly in early hypertrophic cartilage, consistent with immunohistochemical stainings of mouse embryo sections. Furthermore, osteoarthritic chondrocytes, resembling a hypertrophic phenotype, have high AP‐2ε levels. The AP‐2ε promoter harbors binding sites for the transcription factors AP‐2α and Sox9. Both transcription factors strongly activate AP‐2ε expression in a cooperative manner in the chondrosarcoma cell line SW1353. The inhibition of Sox9 expression by small interfering RNA resulted in decreased AP‐2ε expression. In addition, direct interaction of Sox9 with the AP‐2ε promoter could be confirmed by chromatin immunoprecipitation and electromobility shift assays. This is the first study to prove the direct regulation of AP‐2ε by the transcription factor Sox9, and to indicate that AP‐2ε potentially has an important role as a modulator of hypertrophic cartilage.
早期雏鸡肢芽中合成软骨蛋白多糖核心蛋白的细胞群。
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