LncRNA CALB2 sponges miR-30b-3p to promote odontoblast differentiation of human dental pulp stem cells via up-regulating RUNX2
LncRNA CALB2 sponges miR-30b-3p to promote odontoblast differentiation of human dental pulp stem cells via up-regulating RUNX2
复制标题
LncRNA CALB2海绵miR-30b-3p通过上调RUNX2促进人牙髓干细胞的成牙本质细胞分化
DOI：
10.1016/j.cellsig.2020.109695
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发表时间：
2020-09-01
影响因子：
4.8
通讯作者：
Song, Zhi
中科院分区：
文献类型：
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作者：
Tu, Shaoqin;Wu, Jinyan;Song, Zhi
阐明人牙髓干细胞向成牙本质细胞分化的机制是寻找促进牙本质发育治疗线索的关键。LncRNA在成牙本质细胞分化中起调节作用。在这里，我们鉴定了一种新的lncRNA，命名为lncRNA CALB 2。它在成牙本质细胞分化的hDPSC中上调，并可能与miR-30 b-3 p和RUNX 2相互作用。通过功能获得和功能丧失的方法，我们发现lncRNA CALB 2显著促进hDPSCs的成牙本质细胞分化。双荧光素酶报告基因检测和RNA免疫沉淀实验表明，lncRNA CALB 2和RUNX 2 mRNA均能通过相同的结合位点与miR-30 b-3 p直接结合。有趣的是，在成牙本质细胞分化过程中，hDPSC中的miR-30 b-3 p下调，RUNX 2上调。此外，lncRNA CALB 2敲低显著降低了RUNX 2、DSPP和miR-1的蛋白水平，而miR-30 b-3 p抑制剂挽救了这种降低。此外，miR-30 b-3 p对成牙本质细胞分化具有抑制作用，这可以被lncRNA CALB 2逆转。总的来说，这些发现表明新发现的1 ncRNA CALB 2作为miR-30 b-3 p海绵来调节RUNX 2表达，从而促进hDPSC的成牙本质细胞分化。LncRNA CALB 2/miR-30 b-3 p/RUNX 2轴可能成为促进牙体发育的新的治疗靶点。
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.