Epigenetic regulation of dental-derived stem cells and their application in pulp and periodontal regeneration

Chen, Yuyang; Wang, Xiayi; Wu, Zhuoxuan; Jia, Shiyu; Wan, Mei-Hua

doi:10.7717/peerj.14550

Cited by 6 publications

(2 citation statements)

References 161 publications

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“…Epigenetic regulation changes the expression level and function of genes without changing the sequences [ 28 ]. It involves in many biological processes, such as embryonic development, bone homeostasis, and the fate of stem cells [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

METTL3 enhances dentinogenesis differentiation of dental pulp stem cells via increasing GDF6 and STC1 mRNA stability

et al. 2023

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Background The dentinogenesis differentiation of dental pulp stem cells (DPSCs) is controlled by the spatio-temporal expression of differentiation related genes. RNA N6-methyladenosine (m6A) methylation, one of the most abundant internal epigenetic modification in mRNA, influences various events in RNA processing, stem cell pluripotency and differentiation. Methyltransferase like 3 (METTL3), one of the essential regulators, involves in the process of dentin formation and root development, while mechanism of METTL3-mediated RNA m6A methylation in DPSC dentinogenesis differentiation is still unclear. Methods Immunofluorescence staining and MeRIP-seq were performed to establish m6A modification profile in dentinogenesis differentiation. Lentivirus were used to knockdown or overexpression of METTL3. The dentinogenesis differentiation was analyzed by alkaline phosphatase, alizarin red staining and real time RT-PCR. RNA stability assay was determined by actinomycin D. A direct pulp capping model was established with rat molars to reveal the role of METTL3 in tertiary dentin formation. Results Dynamic characteristics of RNA m6A methylation in dentinogenesis differentiation were demonstrated by MeRIP-seq. Methyltransferases (METTL3 and METTL14) and demethylases (FTO and ALKBH5) were gradually up-regulated during dentinogenesis process. Methyltransferase METTL3 was selected for further study. Knockdown of METTL3 impaired the DPSCs dentinogenesis differentiation, and overexpression of METTL3 promoted the differentiation. METTL3-mediated m6A regulated the mRNA stabiliy of GDF6 and STC1. Furthermore, overexpression of METTL3 promoted tertiary dentin formation in direct pulp capping model. Conclusion The modification of m6A showed dynamic characteristics during DPSCs dentinogenesis differentiation. METTL3-mediated m6A regulated in dentinogenesis differentiation through affecting the mRNA stability of GDF6 and STC1. METTL3 overexpression promoted tertiary dentin formation in vitro, suggesting its promising application in vital pulp therapy (VPT).

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Section: Discussionmentioning

confidence: 99%

METTL3 enhances dentinogenesis differentiation of dental pulp stem cells via increasing GDF6 and STC1 mRNA stability

et al. 2023

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“…applications. 22 Since SHED are obtained from deciduous teeth, pediatric dentistry has a crucial role in the extraction of these multipotent cells. 7 DPSC and SHED both are proven to contain the potential to regenerate damaged dental tissue, such as vital and vascularized dental pulp, dentin, and periodontal tissues.…”

Section: Figure 1: Types Of Dental Stem Cells and Theirmentioning

confidence: 99%

Dental stem cells and their applications in pediatric dentistry

Aldomyati,

Alghamdi,

Alzahrani

et al. 2023

Int J Community Med Public Health

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Regenerative medicine has garnered significant attention due to its transformative impact on disease management and the restoration of optimal bodily functions. Stem cells, a cornerstone of regenerative medicine, are particularly renowned for their remarkable capacity to facilitate tissue regeneration and repair, revolutionizing modern healthcare by offering diverse treatment avenues for multiple conditions. Dental pulp stem cells (DPSCs), a subset of postnatal stem cells, are especially noteworthy for their extensive proliferation and ability to differentiate into various specialized cell types. In the realm of pediatric dentistry, there exists a pressing need for advancements in regenerative medicine. Thorough research in this domain has the potential to propel evidence-based pediatric dentistry, ensuring that children receive tailored, high-quality care. Stem cells hold immense promise in pediatric dentistry by offering less invasive and regenerative solutions for a range of childhood dental issues and congenital anomalies. This research, initiated on 04 October 2023, was instigated following an exhaustive review of existing literature utilizing databases like PubMed, Web of Science, and Cochrane. The literature search encompassed a wide array of medical terminologies. Dental stem cells are categorized into four major types: DPSCs, stem cells from human exfoliated deciduous teeth (SHED), stem cells of the apical papilla (SCAP), and periodontal ligament stem cells (PDLSCs). Pediatric dentistry, encompassing endodontics, orthodontics, periodontics, and the treatment of craniofacial defects, stands to benefit significantly from the potential of dental stem cells. The preservation of dental pulp stem cells extracted from deciduous and permanent teeth through tooth banking offers a source for future regenerative therapies. The preservation process involves multiple comprehensive steps. In summary, dental stem cells present a promising avenue within pediatric dentistry, offering multifaceted applications ranging from pulpal regeneration and dentin repair to orthodontic support and the treatment of craniofacial anomalies.

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Periodontists and stem cell‐based therapy for alveolar bone regeneration: A national survey

Kaigler,

Misch,

Alrmali

et al. 2024

Journal of Periodontology

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BackgroundStem cell‐based therapy for bone regeneration has received attention in medical settings but has not yet been used in clinical practice for treating alveolar bone defects. The objectives of this study were to explore whether periodontists had heard about this approach, and if so how, how interested they were to learn about it, which attitudes and behavioral intentions they had related to using stem cell‐based grafting, and what they would like to know before using this approach.MethodsAnonymous survey data were collected from 481 members of the American Academy of Periodontology (response rate: 19.41%).ResultsResponses showed 35.3% had heard about stem cell‐based therapy, mostly from publications (9.6%) and meetings (8.3%); 76.1% wanted to learn about it through in‐person continuing education (CE) courses, 68.6% in online CE courses, and 57.1% from manuals; 73% considered this approach promising; and 54.9% preferred it to traditional approaches. It was important to them that it would result in more bone volume (93%), better bone quality (90.4%), and accelerated healing (83.2%). Also, 60.1% considered it likely/very likely that they would adopt this approach, 54% that patients would prefer it, and 62.1% that it would benefit their practice. When asked what they would like to know about this approach, information about short‐ and long‐term outcomes, cost, and logistical considerations were most frequently named.ConclusionsThese findings provide the basis to develop educational interventions for periodontists about this novel approach and inform future research activities aimed to translate this approach to clinical practice.

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Epigenetic regulation of dental-derived stem cells and their application in pulp and periodontal regeneration

Cited by 6 publications

References 161 publications

METTL3 enhances dentinogenesis differentiation of dental pulp stem cells via increasing GDF6 and STC1 mRNA stability

METTL3 enhances dentinogenesis differentiation of dental pulp stem cells via increasing GDF6 and STC1 mRNA stability

Dental stem cells and their applications in pediatric dentistry

Periodontists and stem cell‐based therapy for alveolar bone regeneration: A national survey

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