DLX3 regulates osteogenic differentiation of bone marrow mesenchymal stem cells via Wnt/β-catenin pathway mediated histone methylation of DKK4
DLX3 regulates osteogenic differentiation of bone marrow mesenchymal stem cells via Wnt/β-catenin pathway mediated histone methylation of DKK4
复制标题
DLX3 通过 Wnt/β-catenin 通路介导的 DKK4 组蛋白甲基化调节骨髓间充质干细胞的成骨分化
DOI：
10.1016/j.bbrc.2019.06.029
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发表时间：
2019-08-13
影响因子：
3.1
通讯作者：
Han, Dong
中科院分区：
文献类型：
--
作者：
Sun, Shichen;Yu, Miao;Han, Dong
目的：远端无同源盒3 （DLX3）是参与骨髓间充质干细胞（BMSCs）成骨分化的重要转录因子。然而，其潜在机制尚不清楚。本研究探讨了DLX3在成骨分化中的潜在机制。方法：利用慢病毒实现DLX3在细胞中的过表达和敲低。采用碱性磷酸酶表达、茜素红染色、实时定量聚合酶链反应（RT-qPCR）、Western blotting和染色质免疫沉淀（ChIP）检测骨髓间充质干细胞成骨分化。结果：DLX3过表达促进骨髓间充质干细胞成骨分化，而DLX3敲低抑制骨髓间充质干细胞成骨分化。RT-qPCR和Western blotting检测显示DLX3通过Wnt/ β -catenin通路调节成骨分化。ChIP-qPCR结果显示，DLX3敲低可通过降低DKK4启动子区域组蛋白H3赖氨酸27三甲基化（H3K27me3）的富集来促进DKK4的表达。结论：我们的数据表明DLX3在BMSCs成骨分化过程中通过组蛋白修饰DKK4调控Wnt/ β -catenin通路。(C) 2019作者。Elsevier Inc.出版。这是一篇基于CC BY-NC-ND许可（http://creativecommons.org/licenses/by-nc-nd/4.0/）的开放获取文章。
Objective: Distal-less homeobox 3 (DLX3) is an important transcription factor involved in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). However, the underlying mechanism is not clear. This study investigated the underlying mechanism of DLX3 in osteogenic differentiation.Methods: DLX3 overexpression and knockdown in cells were achieved using lentiviruses. The osteogenic differentiation of BMSCs was detected using alkaline phosphatase expression, alizarin red staining, real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, and chromatin immunoprecipitation (ChIP) assays.Results: DLX3 overexpression promoted the osteogenic differentiation of BMSCs, whereas DLX3 knockdown reduced the osteogenic differentiation of BMSCs. RT-qPCR and Western blotting assays showed that DLX3 modulated osteogenic differentiation via the Wnt/beta-catenin pathway. ChIP-qPCR showed that DLX3 knockdown promoted DKK4 expression by decreasing the enrichment of histone H3 lysine 27 trimethylation (H3K27me3) in the promotor region of DKK4.Conclusion: Our data implied that DLX3 regulated Wnt/beta-catenin pathway through histone modification of DKK4 during the osteogenic differentiation of BMSCs. (C) 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).