Expression of Clu and Tgfb1 during murine tooth development: effects of in-vivo transfection with anti-miR-214

Expression of Clu and Tgfb1 during murine tooth development: effects of in-vivo transfection with anti-miR-214
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DOI:
10.1111/eos.12056
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发表时间:
2013-08-01
影响因子:
1.9
通讯作者:
Osmundsen, Harald
Osmundsen, Harald
中科院分区:
医学4区
文献类型:
--
作者:
Khan, Qalb-E-Saleem;Sehic, Amer;Osmundsen, Harald

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小鼠第一磨牙牙胚发育过程中Clu的表达明显增加。如前所述,该基因表达的时间过程与编码牙发育分泌期蛋白质的其他基因的表达时间过程一致。小鼠磨牙牙胚中clusterin的免疫组织化学研究表明,这种蛋白质位于外釉上皮,退化的成釉器官,分泌成釉细胞,牙齿连接口腔上皮在早期萌出阶段的牙齿。转化生长因子β-1(TGF-1)的免疫标记显示,它位于clusterin附近。在体内转染抗miR-214后,Clu和Tgfb 1的表达水平显著降低。相反,与生长和发育调节相关的几个基因的表达通过这种处理增加。我们认为,丛生蛋白在分泌牙发生和早期爆发阶段的功能。用抗miR-214处理后的生物信息学分析表明,虽然与牙齿矿化和萌出相关的细胞活性被抑制,但与替代发育活性(即收缩蛋白的生物合成)相关的活性似乎被刺激。这些变化可能是通过一个共同的转录因子群介导的调节发生的,并支持microRNAs(miRNAs)作为牙齿发育过程中分化的调节因子具有高度重要性的建议。
Expression of clusterin (Clu) in the murine first molar tooth germ was markedly increased at postnatal developmental stages. The time-course of expression of this gene paralleled those of other genes encoding proteins involved during the secretory phase of odontogenesis, as described previously. Immunohistochemical studies of clusterin in murine molar tooth germs suggested this protein to be located in outer enamel epithelium, regressing enamel organ, secretory ameloblasts, and the dental epithelium connecting the tooth to the oral epithelium at an early eruptive stage. Immunolabelling of transforming growth factor beta-1 (TGF-1) revealed it to be located close to clusterin. The levels of expression of Clu and Tgfb1 were markedly decreased following in-vivo transfection with anti-miR-214. In contrast, the expression of several genes associated with regulation of growth and development were increased by this treatment. We suggest that clusterin has functions during secretory odontogenesis and the early eruptive phase. Bioinformatic analysis after treatment with anti-miR-214 suggested that, whilst cellular activities associated with tooth mineralization and eruption were inhibited, activities associated with an alternative developmental activity (i.e. biosynthesis of contractile proteins) appeared to be stimulated. These changes probably occur through regulation mediated by a common cluster of transcription factors and support suggestions that microRNAs (miRNAs) are highly significant as regulators of differentiation during odontogenesis.