Shared Genetic and Epigenetic Mechanisms between the Osteogenic Differentiation of Dental Pulp Stem Cells and Bone Marrow Stem Cells.

Sebastian Gaus,Vuk Savkovic,Sebastian Hahnel,Gerhard Schmalz,Dirk Ziebolz,Tina Kottek,Xiangqiong Liu,Yupei Deng,Simin Li,Qian Wang,Hanluo Li,Rainer Haak,Lei Liu,Bernd Lethaus,Min Tang

doi:10.1155/2021/6697810

Abstract

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.

Highlights

Repairing bone defects remains a challenge for clinical practitioners to the present day
The GSE138180 dataset reported the miRNA expression alteration of dental pulp stem cells (DPSC) investigated by comparing the 14th day of postdifferentiation with the 14th day of culturing cells without differentiation
After performing Differential expression analysis (DEA) based on two datasets (GSE138180 and GSE107279), 186 DEmiRNAs (122 upregulated and 64 downregulated) and 104 DEmiRNAs (52 upregulated and 52 downregulated) were identified as differentially expressed in the osteogenic differentiation processes of DPSC and bone marrow stem cells (BMSC), respectively

Summary

Introduction

Repairing bone defects remains a challenge for clinical practitioners to the present day. BioMed Research International stem cells appear to be a good match to the unmet needs of the conventional autologous bone transplantation. They are capable of acting in paracrine anti-inflammatory and trophic fashion, as well as of providing a cellular base for tissue replacement by virtue of their self-renewal and multilineage differentiation capacity [4]. BMSCs have been the most commonly used type of stem cells for osteogenesis and new bone formation due to their tissue origin; BMSCs are obtained by means of invasive and painful bone marrow aspiration [5]. Critical preclinical data necessary for understanding the genetic and epigenetic mechanisms involved in the osteogenic differentiation of DPSCs and BMSCs are still modestly represented

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Discussion

Conclusion