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首页> 外文期刊>Cell and Tissue Research >lncRNA DANCR suppresses odontoblast-like differentiation of human dental pulp cells by inhibiting wnt/beta-catenin pathway
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lncRNA DANCR suppresses odontoblast-like differentiation of human dental pulp cells by inhibiting wnt/beta-catenin pathway

机译:lncRNA DANCR通过抑制wnt /β-catenin途径抑制人牙髓细胞的成牙本质细胞样分化

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Long noncoding RNAs (lncRNAs) have recently emerged as an important class of regulatory molecules in diverse biological processes, although lncRNA involvement in the odontoblast-like differentiation of human dental pulp cells (hDPCs) is poorly understood. We investigate the expression of lncRNAs in this differentiation and explore their underlying role and the involved mechanism. Integrated comparative lncRNA microarray profiling was used to examine lncRNA expression during this differentiation. The differential expression of lncRNAs was validated by quantitative real-time reverse transcription plus the polymerase chain reaction. Differential lncRNA overexpression was performed with an adenoviral vector and the role and mechanism was then investigated in odontoblast-like differentiation. We identified 139 differentially expressed lncRNAs during this differentiation. Among them, five lncRNAs differentially expressed in microarray analysis were validated. Notably, lncRNA DANCR expression was significantly downregulated during hDPC differentiation to odontoblast-like cells in a time-dependent manner. Moreover, lncRNA DANCR overexpression blocked mineralized nodule formation and the expression of DSPP and DMP-1 in hDPCs after 14 days of odontogenic induction. Importantly, the upregulation of DANCR significantly decreased the expression levels of p-GSK-3 beta and beta-catenin expression indicating that lncRNA DANCR can inhibit the activation of the Wnt/beta-catenin signal pathway during the odontoblast-like differentiation of hDPCs. Thus, the modulation of Wnt/beta-catenin signaling by lncRNA DANCR represents a potential therapeutic option for reparative dentin formation and regenerative endodontics.
机译:长的非编码RNA(lncRNA)最近已成为各种生物过程中的重要一类调节分子,尽管对lncRNA参与人牙髓细胞(hDPC)的成牙本质样分化的了解很少。我们调查了这种分化中lncRNAs的表达,并探讨了它们的潜在作用和所涉及的机制。整合的比较性lncRNA微阵列分析用于检查这种分化过程中lncRNA的表达。通过定量实时逆转录加聚合酶链反应验证了lncRNA的差异表达。用腺病毒载体进行lncRNA差异表达,然后研究其在成牙本质细胞样分化中的作用和机制。在这种分化过程中,我们鉴定了139个差异表达的lncRNA。其中,验证了在微阵列分析中差异表达的五个lncRNA。值得注意的是,在hDPC分化为成牙本质细胞样细胞的过程中,lncRNA DANCR表达以时间依赖性方式显着下调。此外,在牙源性诱导14天后,lncRNA DANCR的过表达阻断了hDPC中矿化的结节形成以及DSPP和DMP-1的表达。重要的是,DANCR的上调显着降低了p-GSK-3β和β-catenin的表达水平,表明lncRNA DANCR可以抑制成牙本质细胞样hDPC分化过程中Wnt /β-catenin信号通路的激活。因此,lncRNA DANCR对Wnt /β-catenin信号传导的调节代表修复性牙本质形成和再生牙髓的潜在治疗选择。

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