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LncRNA CALB2 sponges miR-30b-3p to promote odontoblast differentiation of human dental pulp stem cells via up-regulating RUNX2

机译:LNCRNA CALB2海绵MIR-30B-3P通过UP-COMMETION RUNX2促进人牙髓干细胞的Odontoblast分化

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摘要

Illuminating the mechanisms of odontoblast differentiation of human dental pulp stem cells (hDPSCs) is the key to find therapeutic clues to promote odontogenesis. LncRNAs play a regulatory role in odontoblast differentiation. Here, we identified a novel lncRNA, named lncRNA CALB2. It was up-regulated in odontoblast-differentiated hDPSCs and potentially interacted with miR-30b-3p and RUNX2. Via gain- and loss-of-function approaches, we found lncRNA CALB2 significantly promoted the odontoblast differentiation of hDPSCs. Then, dual luciferase reporter assay and RNA immunoprecipitation assay revealed that both lncRNA CALB2 and RUNX2 mRNA could directly bind to miR-30b-3p via the same binding sites. Interestingly, miR-30b-3p in hDPSCs was down-regulated and RUNX2 was up-regulated during odontoblast differentiation. Moreover, lncRNA CALB2 knockdown significantly reduced the protein level of RUNX2, DSPP and DMP-1, while miR-30b-3p inhibitor rescued the reduction. Furthermore, miR-30b-3p exerted an inhibitory effect on odontoblast differentiation, which could be reversed by lncRNA CALB2. Collectively, these findings indicate that the newly identified 1ncRNA CALB2 acts as a miR-30b-3p sponge to regulate RUNX2 expression, thus promoting the odontoblast differentiation of hDPSCs. LncRNA CALB2/miR-30b-3p/RUNX2 axis could be a novel therapeutic target for accelerating odontogenesis.
机译:照亮人牙齿牙髓干细胞(HDPSC)的异常子细胞分化的机制是寻找治疗线索以促进牙核发生的关键。 LNCRNA在Odontoblast分化中发挥着监管作用。在这里,我们鉴定了一个名为lncrna calb2的新型lncrna。它在odontoblast差异化的HDPSC中上调,可能与miR-30b-3p和runx2相互作用。通过增益和丧失函数的方法,我们发现LNCRNA CALB2显着促进了HDPSC的异常子细胞分化。然后,双荧光素酶报告器测定和RNA免疫沉淀测定显示,LNCRNA CALB2和RUNX2 mRNA可以通过相同的结合位点直接与miR-30b-3p结合。有趣的是,HDPSC中的miR-30b-3p被下调,并且在Odontoblast分化期间runx2上调。此外,LNCRNA CALB2敲低显着降低了RUNX2,DSPP和DMP-1的蛋白质水平,而MIR-30B-3P抑制剂救出了减少。此外,miR-30b-3p对Odontoblast分化的抑制作用施加了抑制作用,其可以通过LNCRNA CALB2逆转。总的来说,这些发现表明,新鉴定的1ncRNA CALB2用作MIR-30B-3P海绵,以调节RUNX2表达,从而促进HDPSC的异藤细胞分化。 LNCRNA CALB2 / MIR-30B-3P / RUNX2轴可以是用于加速odontogens的新型治疗靶标。

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  • 来源
    《Cellular Signalling》 |2020年第1期|共10页
  • 作者单位

    Sun Yat Sen Univ Hosp Stomatol Guanghua Sch Stomatol Guangdong Prov Key Lab Stomatol Guangzhou 510055 Guangdong Peoples R China;

    Sun Yat Sen Univ Hosp Stomatol Guanghua Sch Stomatol Guangdong Prov Key Lab Stomatol Guangzhou 510055 Guangdong Peoples R China;

    Sun Yat Sen Univ Hosp Stomatol Guanghua Sch Stomatol Guangdong Prov Key Lab Stomatol Guangzhou 510055 Guangdong Peoples R China;

    Hainan Med Univ Hainan Gen Hosp Dept Stomatol Hainan Affiliated Hosp Haikou 570311 Hainan Peoples R China;

    Sun Yat Sen Univ Hosp Stomatol Guanghua Sch Stomatol Guangdong Prov Key Lab Stomatol Guangzhou 510055 Guangdong Peoples R China;

    Sun Yat Sen Univ Hosp Stomatol Guanghua Sch Stomatol Guangdong Prov Key Lab Stomatol Guangzhou 510055 Guangdong Peoples R China;

    Sun Yat Sen Univ Hosp Stomatol Guanghua Sch Stomatol Guangdong Prov Key Lab Stomatol Guangzhou 510055 Guangdong Peoples R China;

    Sun Yat Sen Univ Hosp Stomatol Guanghua Sch Stomatol Guangdong Prov Key Lab Stomatol Guangzhou 510055 Guangdong Peoples R China;

    Sun Yat Sen Univ Hosp Stomatol Guanghua Sch Stomatol Guangdong Prov Key Lab Stomatol Guangzhou 510055 Guangdong Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞形态学;
  • 关键词

    Dental pulp stem cells; Odontoblast differentiation; LncRNA CALB2; MiR-30b-3p; Competing endogenous RNAs;

    机译:牙髓干细胞;Odontoblast分化;lncrna calb2;mir-30b-3p;竞争内源性RNA;

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