Table 1.
The current studies of epigenetic regulation of dental stem cells in regenerative medicine.
| Cell type | Method | Outcomes | Ref/year |
|---|---|---|---|
| Induced pluripotent stem cell (iPS cell) generation from dental pulp stem cells (DPSCs) | A reprogramming scheme was investigated for iPS generation from DPSCs | Sufficient iPS cell generation from DPSCs, improving clinical and industrial utilization of iPS knowledge to use in therapies | [53]/2018 |
| DPSCs | Examination of regulating Notch/Wnt signaling and stimulation of adipo-/osteocytes differentiation in DPSC cell lines | Wnt signaling could participate in the safer progression and lower destructive reprogramming platforms in DPSCs to utilize in cell therapy | [35]/2020 |
| DPSCs and bone marrow-derived mesenchymal stem cells (BMSCs) | Examination of similar genetic and epigenetic mechanisms between the osteogenic differentiation of DPSCs and BMSCs | Common epigenetic and genetic mechanisms are concluded in the osteogenic differentiation of BMSCs and DPSCs | [54]/2021 |
| Human MSCs | Identification of miR-34a aims protein systems as an osteoblastic regulator of [51] human MSC differentiation | miRNA-34a showed particular dual modulatory impacts on both proliferation and differentiation of human MSC. Additionally, miR-34a suppression could be a novel therapeutic approach for increasing the formation of bone tissue | [55]/2014 |
| BMSCs were isolated from C57/BL mice | Investigation of miRNA function in the regulation of osteogenesis procedure in the inflammatory condition | miR-34a reverses proinflammatory cytokine effects and stimulates osteogenic differentiation, exhibiting that therapy based on miR-34a might be a suitable method for stimulating the regeneration of bone tissues | [39]/2019 |
| Human DPSCs | Evaluation of different differentiation circumstances. K+ channels initiation is assumed to modulate the Ca2+ content, which is intracellular, tolerating to change cell cycle to human DPSC differentiation induction | Epigenetic reprogramming and cell cycle regulation via a promotion with remarkable K+ facilitated differentiation of human DPSCs into neuron-like cells. Hence, human DPSCs have the practical function as neuron-like cells via alteration of cells cycle | [56]/2020 |
| Human DSCs | Investigation regulating the specification of signals tissue and lineage of cells epigenetically through evaluation of miRNA activity behind dental stem cells (DSCs) | miRNA-modulated pathway for the human DSC differentiation and a chosen network of miRNAs that control DSC osteogenic differentiation | [57]/2014 |
| DPSCs | Investigation of immunomodulatory abilities of DPSCs by cocultured from elderly and young donors | Decrement of IL-6 and HGF expressions are necessary for the bone and dental tissue regeneration and downregulate highly in elder DPSCs | [58]/2021 |
| DPSCs | Assessment of multipotential differentiation abilities of DPSCs | Ferutinin activated and promoted osteogenic differentiation of DPSCs, as a promising effective stem cell therapy for osteoporosis | [59]/2020 |
| DPSCs | Explore the osteogenic, adipogenic, and resistance to oncogenic transformation of DPSCs in comparison with BMSCs | Several epigenetic factors widely implied tumorigenesis lineage and commitment, which might be considered when progressing stem cell therapeutic uses | [4]/2019 |
| Periodontal ligament stem cells (PDLSCs) | To characterize DPSCs and their mechanism of differentiation cells from human DPSCs and PDLSCs, explore a miRNA array based on LNA | miR-720 reduced DPSC proliferation as distinguished via immunocytochemical assessment against ki-67 and stimulated odontogenic differentiation, like Alkaline phosphatase and mRNA levels of osteopontin. Also, outcomes demonstrated that miR-720 is a modulator miRNA for the DPSC differentiation | [60]/2013 |
| Human DPSCs | Odontoblast-related genes changes were explored epigenetically via the alteration of the mitogen-activated protein kinase (MAPK) signaling pathway in cell lines | Cell proliferation downregulated response to MS-275 using, while it did not affect cytotoxicity in 5 and 10 nM and induced odontoblast-like cells differentiation | [61]/2020 |
| DSCs | Evaluate KDM6B knockdown in DSCs and its effect on Alkaline phosphatase function and mineralized nodules formation | Outcomes exhibited participation of HDMs in the epigenetic modulation of odontogenic differentiation of DSCs. Lysine demethylase 6B (KDM6B) may indicate a promising beneficial aim in the tooth repairment and regeneration of craniofacial tissues | [62]/2013 |
| DPSCs | N6-methyladenosine (m6A) methylation biological actions were assessed in DPSCs | m6A methylated hallmarks in DPSCs and modulatory participation in the cells cycle. It can use as a therapeutic approach in vital pulp therapy | [63]/2021 |
| Mesenchymal stem cells (MSCs) derived from bone marrow and dental tissues | Address the function of long noncoding RNAs (lncRNAs) in osteogenesis modulation of MSCs derived from bone marrow and dental tissues. Also, lncRNAs as therapeutic aims for MSC-related diseases were investigated | lncRNAs involved in the bone marrow and dental tissue-derived MSCs' osteogenic differentiation could aim as prognosis and therapeutic parameters. Nevertheless, the lncRNA precise actions remain elusive | [64]/2018 |
| MSCs | Investigate trichostatin A effects on osteogenic differentiation and resolve inflammation on MSCs derived from inflamed and normal gingival tissues | Anti-inflammatory properties and stimulation repairment of periodontal tissue were shown via trichostatin A as a candidate for therapeutic approaches in repairing periodontal tissues | [65]/2020 |
| DPSCs | Explore genome-wide gene expression microarray and DNA methylome investigation to clarify molecular changes by DNA methylation alterations correlated with DPSC exposure to ethanol | Findings proved that significant alcohol usage might affect cellular processes that cause decreased mineral deposition, resulting in osteoporosis/-penia, dental abnormalities, and hallmark conditions for different fetal conditions induced via alcohol | [23]/2016 |
| DPSCs | Examine the interference with N6-adenosine-methyltransferase 70 kDa subunit (METTL3) in DPSCs inhibits cell proliferation and osteogenic differentiation | Findings provide new ideas for using stem cells in clinical applications and for treating metabolic bone diseases by altering epigenetic modifications | [66]/2021 |
| Human DPSCs | H19 mechanisms and impacts were assessed in human DPSC odontogenic differentiation | Provide novel visions of how the S-adenosylhomocysteine hydrolase (SAHH)/H19 axis functions in the odontogenic differentiation of human DPSCs. It would help develop therapies for the regeneration of dentin following stem cells | [67]/2018 |
| Human dental follicle stem cells (DFSCs) | Examine Enhancer Of Zeste 2 Polycomb Repressive Complex 2 Subunit (EZH2) and histone H3 lysine 27 (H3K27) trimethylation expression during osteogenesis of human DFSCs | EZH2 promoted the Wnt/β-catenin pathway by modulating the level of H3K27 trimethylation on stimulators of genes in these signaling pathways | [68]/2018 |
| Human DPSCs | Assessment of trichostatin A on differentiation and proliferation of odontoblast along with its capacity in the forming of dentin and odontoblast differentiation in vivo during tooth progression | Trichostatin A conducted vital function in odontoblast differentiation and proliferation of human DPSCs in dental progression phases | [69]/2013 |
| DSCs | Investigate the DSC niche cell types and the miR-200 class effects on the fates of DSCs | miR-200 modulates signaling pathways necessities for cell differentiation, progression of the cell cycle, and DSC niche maintenance | [70]/2021 |
| DPSCs | Evaluate the regulatory role of Krüppel-like factor 2 (KLF2) during osteoblast DPSCs differentiation via assessing the KLF2 levels and autophagy-related molecules in cells | Chromatin immunoprecipitation evaluation showed that the functional epigenetic biomarkers and KLF2 were elevated in the stimulator region of autophagy-related 7 (ATG7) | [71]/2020 |
| Human DFSCs | Investigate genes' functions and regulatory mechanisms (HOXA transcript antisense RNA, myeloid-specific 1 (HOTAIRM1), and homeobox A (HOXA)) in human DFSCs | HOTAIRM1 stimulated the human DFSC osteogenesis via modulating homeobox A2 (HOXA2) through DNA methyltransferase 1 (DNMT1). HOXA2 exhibited necessary actions in human DFSCs, same as HOTARIM1. Nonetheless, the HOTARIM1 modulatory pattern within the HOXA group remains unknown | [72]/2020 |
| Mice DPCs | Identify Spalt-like transcription factor 1 (SALL1), polarizing and secretory odontoblasts, in vivo | SALL1 effectively modulates the odontoblast lineages commitment via connection with runt-related transcription factor 2 (RUNX2) and straight activation of transforming growth factor beta-2 (TGFβ-2) at an initial phase | [73]/2021 |
| Human DPSCs and BMSCs | Investigate corepressor CBFA2/RUNX1 partner transcriptional corepressor 2 (CBFA2T2) expression was remarkably increased in response to BMP2 treatment during osteogenic differentiation of human DPSCs and BMSCs | CBFA2T2 is required for BMP2-induced osteogenic differentiation of MSCs by inhibiting euchromatic histone lysine methyltransferase 1- (EHMT1-) mediated histone methylation at RUNX2 stimulator | [74]/2018 |
| Human DPSCs | Histone H3 lysine 4 (H3K4) trimethylation and H3K27 trimethylation spatiotemporal patterns were examined in the mice model. Human DPSCs induced during odontogenic differentiation, H3K27 trimethylation demethylases (UTX and JMJD3), and H3K4 trimethylation methylases | During dental MSCs differentiation, Wnt family member 5A (WNT5A) transcription activities were modulated via stability among H3K27 trimethylation/H3K4 trimethylation, Jumonji domain-containing protein-3, and H3K4 trimethylation methylase stimulator | [75]/2018 |
| Human DFSCs | Explore the osteogenic differentiation of human DFSCs and chromodomain helicase DNA binding protein 7 (CHD7) expression | CHD7 regulates the osteogenic differentiation of human hepatocytes by modulating the transcription of parathyroid hormone 1 receptor (PTH1R). Also, overexpression of PTH1R partially restores osteogenic differentiation in CHD7-knockdown human DFSCs | [76]/2020 |
| Human DPSCs | Investigate the photobiomodulation therapy (PBMT) role on viability, human DPSCs migration, and its correlation to epigenetic mechanisms such as acetylation of histones | There is a correlation between PBMT and high viability and human DPSCs migration, related to the histone acetylation upregulation. Also, PBMT is an appealing adjuvant therapy for regenerative endodontic treatment | [77]/2020 |
| Human DPSCs | Evaluate epigenetic reprogramming via the histone deacetylase 3 (HDAC3) and histone deacetylase 2 (HDAC2) selective inhibitors, MI192, to stimulate the osteogenic capacity of human DPSCs for bone regeneration | By reprogramming epigenetic factors of hDPSCs with HDAC2- and HDAC3-specific inhibitors, MI192 improves osteogenic differentiation, implying the feasibility of this method for bone augmentation | [78]/2021 |
| Dental pulp and dental follicles | Differentiation profiles and epigenetic states of dental follicle/dental pulp, two odontogenic neural crest-derived ancestor populations, were examined | The results showed to highlight the crucial function that epigenetic regulation conducts in the odontogenic terminal differentiation neural crest cells | [79]/2013 |
| PDLSCs | Examine the periodontal regeneration effect on the heterogeneous nuclear ribonucleoprotein L (HNRNPL) mechanism in the osteogenesis of PDLSCs induced by strontium chloride (SrCl2) | There may be some implications for the treatment of periodontitis patients who have osteoporosis simultaneously by understanding the different functions of HNRNPL and SET domain containing 2, histone lysine methyltransferase (SETD2) | [80]/2019 |
| PDLSCs | Assess the lysine demethylase 6A (KDM6A) function in chondrogenic differentiation of PDLSCs and the underlying mechanisms related to epigenetic | In the destruction of inflammatory tissue such as osteoarthritis, it was expected an improvement in MSC-mediated regeneration of cartilage through upregulation of KDM6A or the use of EZH2-inhibitors | [81]/2018 |
| Cranial neural crest cells | Kat2a and 2b genes function as histone acetyltransferases and were examined in the progression of craniofacial in zebrafish and the Gcn5 in mice | As a result of regulating H3K9 acetylation, these outcomes proposed that Kat2a and 2b are essential to the growth and cartilage and bone differentiation in both mice and zebrafish | [82]/2018 |