牙髓干细胞和成骨髓干细胞成骨分化的共享遗传和表观遗传机制。
Shared Genetic and Epigenetic Mechanisms between the Osteogenic Differentiation of Dental Pulp Stem Cells and Bone Marrow Stem Cells.
机构信息
Department of Cranio Maxillofacial Surgery, University Clinic Leipzig, Liebigstr. 12, Leipzig 04103, Germany.
Department of Cariology, Endodontology and Periodontology, University Leipzig, Liebigstr. 12, Leipzig 04103, Germany.
出版信息
Biomed Res Int. 2021 Feb 5;2021:6697810. doi: 10.1155/2021/6697810. eCollection 2021.
OBJECTIVE
To identify the shared genetic and epigenetic mechanisms between the osteogenic differentiation of dental pulp stem cells (DPSC) and bone marrow stem cells (BMSC).
MATERIALS AND METHODS
The profiling datasets of miRNA expression in the osteogenic differentiation of mesenchymal stem cells from the dental pulp (DPSC) and bone marrow (BMSC) were searched in the Gene Expression Omnibus (GEO) database. The differential expression analysis was performed to identify differentially expressed miRNAs (DEmiRNAs) dysregulated in DPSC and BMSC osteodifferentiation. The target genes of the DEmiRNAs that were dysregulated in DPSC and BMSC osteodifferentiation were identified, followed by the identification of the signaling pathways and biological processes (BPs) of these target genes. Accordingly, the DEmiRNA-transcription factor (TFs) network and the DEmiRNAs-small molecular drug network involved in the DPSC and BMSC osteodifferentiation were constructed.
RESULTS
16 dysregulated DEmiRNAs were found to be overlapped in the DPSC and BMSC osteodifferentiation, including 8 DEmiRNAs with a common expression pattern (8 upregulated DEmiRNAs (miR-101-3p, miR-143-3p, miR-145-3p/5p, miR-19a-3p, miR-34c-5p, miR-3607-3p, miR-378e, miR-671-3p, and miR-671-5p) and 1 downregulated DEmiRNA (miR-671-3p/5p)), as well as 8 DEmiRNAs with a different expression pattern (i.e., miR-1273g-3p, miR-146a-5p, miR-146b-5p, miR-337-3p, miR-382-3p, miR-4508, miR-4516, and miR-6087). Several signaling pathways (TNF, mTOR, Hippo, neutrophin, and pathways regulating pluripotency of stem cells), transcription factors (RUNX1, FOXA1, HIF1A, and MYC), and small molecule drugs (curcumin, docosahexaenoic acid (DHA), vitamin D3, arsenic trioxide, 5-fluorouracil (5-FU), and naringin) were identified as common regulators of both the DPSC and BMSC osteodifferentiation.
CONCLUSION
Common genetic and epigenetic mechanisms are involved in the osteodifferentiation of DPSCs and BMSCs.
目的
鉴定牙髓干细胞（DPSC）和骨髓间充质干细胞（BMSC）成骨分化过程中的共享遗传和表观遗传机制。
材料与方法
在基因表达综合数据库（GEO）中搜索牙髓间充质干细胞（DPSC）和骨髓间充质干细胞（BMSC）成骨分化的 miRNA 表达谱数据集。通过差异表达分析，确定 DPSC 和 BMSC 成骨分化过程中失调的差异表达 miRNA（DEmiRNAs）。鉴定 DEmiRNAs 调控的靶基因，再鉴定这些靶基因的信号通路和生物过程（BPs）。据此，构建 DPSC 和 BMSC 成骨分化中涉及的 DEmiRNA-转录因子（TFs）网络和 DEmiRNAs-小分子药物网络。
结果
在 DPSC 和 BMSC 成骨分化中发现 16 个重叠的失调 DEmiRNAs，包括 8 个具有共同表达模式的 DEmiRNAs（8 个上调的 DEmiRNAs（miR-101-3p、miR-143-3p、miR-145-3p/5p、miR-19a-3p、miR-34c-5p、miR-3607-3p、miR-378e、miR-671-3p 和 miR-671-5p）和 1 个下调的 DEmiRNA（miR-671-3p/5p）），以及 8 个具有不同表达模式的 DEmiRNAs（即 miR-1273g-3p、miR-146a-5p、miR-146b-5p、miR-337-3p、miR-382-3p、miR-4508、miR-4516 和 miR-6087）。鉴定到几个信号通路（TNF、mTOR、Hippo、neutrophin 和调节干细胞多能性的通路）、转录因子（RUNX1、FOXA1、HIF1A 和 MYC）和小分子药物（姜黄素、二十二碳六烯酸（DHA）、维生素 D3、三氧化二砷、5-氟尿嘧啶（5-FU）和柚皮苷）作为 DPSC 和 BMSC 成骨分化的共同调控因子。
结论
牙髓干细胞和成骨细胞的成骨分化涉及共同的遗传和表观遗传机制。
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