Zhipeng Fan1,2*- 1Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China
- 2Research Unit of Tooth Development and Regeneration, Chinese Academy of Medical Sciences, Beijing, China
Editorial on the Research Topic
Epigenetic Regulation of Stem Cells Derived From Craniofacial Tissues
The function regulation of mesenchymal stem cells (MSCs) is a complex process, and the effects of the directed differentiation of mesenchymal stem cells and the craniofacial tissue regeneration under micro-environmental conditions such as inflammation, hypoxia and aging are not clear, in which epigenetics plays a significant role (1). In this special topic, we have included seven articles that reviewed recent progress in epigenetic regulation of stem cells derived from craniofacial tissues.
Li et al. summarized epigenetic influence on stem cells derived from dental tissues (DSCs). They discussed the important role of epigenetics in odontogenic/osteogenic differentiation of DSCs, DNA methylation, histone modifications, histone acetylation and non-coding RNAs are emphatically introduced. Further, Li illustrated epigenetics affects the odontogenic and osteogenic differentiation of DSCs by regulating signaling pathways.
Han and Fan review of the recent work on the relationship of miRs and osteogenic differentiation of mesenchymal stem cells. MicroRNAs are broadly expressed and involved in stem cell renewal, differentiation, cell cycle and cell apoptosis and other biological processes. miRNAs generally act as an inhibitory molecule by post-transcriptional targeting downstream genes, leading to translational inhibition or mRNA decay. In this review, Fan et al. summarized targeting osteogenic genes regulated by miRNA, in which the major osteogenic transcription factors RUNX2 and OSX were described in detail. Then the authors discussed the influence of miRNAs on the expression levels of Wnt signaling pathway, TGF-β/BMP signaling pathway, MAPK signaling pathway and Notch signaling pathway, which regulate osteogenic differentiation.
Microenvironment also play critical roles in tissue regeneration. Li et al. discussed immune microenvironment and bone regeneration process in oral and maxillofacial region. Bone is composed of osteoblasts, osteoclasts, osteocytes, and other basic elements. Bone resorption and bone formation are largely regulated by a variety of immune responses under normal and pathogenic conditions. In addition to the traditional bone cells, immune cells containing neutrophils, B cells, macrophages and T cells, were also implicated in remodeling of bone. Therefore, interaction between local stem cells and immune cells in the oral microenvironment may modify the regenerative process. Cytokines are derived from immunocompetent cells such as TNFα, IL-1, IL-6 and interferon-γ (IFN-γ). At last, Yu revealed the effects of these inflammatory cytokines on both osteoclasts (OC) and osteoblasts.
Hypoxia is an important cellular stress mechanism with significant pathological implications in numerous diseases. Ye et al. also discussed that tissue regeneration is modulated by different Non-coding RNAs (ncRNAs) in hypoxia. They summarized the effects of hypoxia on the proliferation and differentiation potential of odontogenic MSCs, and also pointed out the results are uncertain due to the differences of cell sources and experimental conditions. The authors further discussed the effect of hypoxia-induced ncRNAs on differentiation of mesenchymal stem cells. Studies of ncRNAs and their interaction can promote or reverse the effects of hypoxia microenvironment on MSCs, and provide good conditions for better modified stem cells for in vivo transplantation.
In addition, ncRNAs derived from extracellular vesicle has become the focus of cell-to-cell communication, which play an essential role in regulating different biological processes. Yan et al. reviewed the research progress of extracellular vesicle (EV) secreted by MSCs (MSC-EVS) in tooth and maxillofacial tissue repair and regeneration. They reviewed the achievement and methodology of EV derived ncRNA. They discussed the expression of ncRNA in EV cells from different MSCs and cell modification triggers EV transfer of ncRNAs. Emerging evidence confirmed that EV-derived ncRNA can efficiently modulate the differentiation of MSC. These EV derived non-coding RNAs have the potential to be used as drug vehicle.
MSCs are promising candidates for cellular therapy of different diseases in humans and in animals. Zhang et al. reviewed the literature on stem cell therapy in chronic periodontitis and summarized limitations from the host and coping strategies that influence resident or transplanted stem cell-mediated periodontal regeneration. PDLSCs have been proved to possess the periodontal regenerative property in vitro and animal studies, however the clinical application of autologous PDLSCs to treat periodontal intrabony defects is not satisfactory, which indicates continuous inflammation in the periodontal tissue induces functional impairments of endogenous P-PDLSCs. The prerequisite for stem cell therapy in chronic periodontitis is the improvement of local stem cell niche. Small molecular drugs, herbal extracts, and accessory extracellular vesicle products, can effectively improve the extracellular environment and promote stem cell function. And they also mentioned that active treatments for systemic diseases would also assist in recovering the limited stem cell function on the basis of amelioration of the inflammatory periodontal microenvironment.
Another type of MSCs that have been broadly mentioned is stem cells derived from human exfoliated deciduous teeth. Guo et al. state the multipotency of SHEDs in their review, presenting the immense potential for tissue regeneration engineering. And they emphatically introduce the paracrine activity and immunomodulatory of SHEDs, it can interact with the local inflammatory microenvironment through multiple paracrine functions, and the modulatory functions of SHEDs-CM or SHED-EVs to immunocyte have been proved as well. All these biological properties indicate SHEDs will be widely used in clinical application in regenerative medicine.
Author Contributions
ZF: design and conception, manuscript writing, manuscript revising, financial support, final approval of the manuscript, and approved publication.
Funding
This work was supported by the State Key Program of National Sciences Foundation of China (82130028 to ZF).
Conflict of Interest
The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's Note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
Keywords: mesenchymal stem cells, epigenetic, differentiation, regeneration, microenvironment
Citation: Fan Z (2022) Editorial: Epigenetic Regulation of Stem Cells Derived From Craniofacial Tissues. Front. Dent. Med. 3:911510. doi: 10.3389/fdmed.2022.911510
Received: 02 April 2022; Accepted: 28 April 2022;
Published: 20 May 2022.
Edited and reviewed by: Paul Sharpe, King's College London, United Kingdom
Copyright © 2022 Fan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Zhipeng Fan, zpfan@ccmu.edu.cn