Molecular and circadian controls of ameloblasts.

Molecular and circadian controls of ameloblasts.
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DOI:
10.1111/j.1600-0722.2011.00918.x
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发表时间:
2011-12
影响因子:
1.9
通讯作者:
Papagerakis P
Papagerakis P
中科院分区:
医学4区
文献类型:
--
作者:
Athanassiou-Papaefthymiou M;Kim D;Harbron L;Papagerakis S;Schnell S;Harada H;Papagerakis P

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成釉细胞特异性基因的阶段特异性表达受转录因子的差异表达控制。此外,成釉细胞在其主要活动中遵循每日节律,即釉质蛋白分泌和釉质矿化。这种与时间相关的控制是由参与昼夜节律调节的时钟蛋白的振荡所协调的。我们的目的是确定成釉细胞分化的日常节律和发育控制之间的潜在联系。在HAT-7成釉细胞系中评价了选定的转录因子Distal-less homeobox 3(Dlx 3)和Runt相关转录因子2(Runx 2)以及时钟基因核受体亚家族1,D组,成员1(Nr 1d 1)对分泌和成熟成釉细胞的影响[使用阶段特异性标记物釉原蛋白(Amel)、釉蛋白(Enam)和激肽释放酶相关肽酶4(Klk 4)]。Amel和Enam稳态RNA表达水平在Runx 2过表达细胞中下调,在Dlx 3过表达细胞中上调。相反,Klk 4被Dlx 3和Runx 2上调。此外,时钟基因和成釉细胞分化标志物之间的时间和空间的关系进行了检测。有趣的是,时钟基因不仅影响成釉细胞特异性基因的节律表达,而且还影响Runx 2的表达。多尺度的数学建模正在探索,以进一步了解成釉细胞分化的时间和发育控制。我们的研究为维持成釉细胞分化的调控机制提供了新的见解。
Stage-specific expression of ameloblast-specific genes is controlled by differential expression of transcription factors. In addition, ameloblasts follow daily rhythms in their main activities i.e. enamel protein secretion and enamel mineralization. This time related control is orchestrated by oscillations of clock proteins involved in circadian rhythms regulation. Our aim was to identify the potential links between daily rhythms and developmental controls of ameloblast differentiation. The effects of selected transcriptional factors Distal-less homeobox 3 (Dlx3) and Runt related transcription factor 2 (Runx2) and clock gene Nuclear receptor subfamily 1, group D, member 1 (Nr1d1) on secretory and maturation ameloblasts [using stage-specific markers amelogenin (Amel), enamelin (Enam) and kallikrein related-peptidase 4 (Klk4)] were evaluated in HAT-7 ameloblast cell line. Amel and Enam steady-state RNA expression levels were down-regulated in Runx2 over-expressing cells and up-regulated in Dlx3 over-expressing cells. In contrast, Klk4 was up-regulated by both Dlx3 and Runx2. Furthermore, a temporal and spatial relationship between clock genes and ameloblast differentiation markers was detected. Of interest, clock genes not only affected rhythmic expression of ameloblast specific genes but also influenced the expression of Runx2. Multi-scale mathematical modeling is being explored to further understand the temporal and developmental controls of ameloblast differentiation. Our study provides novel insights into the regulatory mechanisms sustaining ameloblast differentiation.
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