The Epigenetic Regulation in Tooth Development and Regeneration

Lin, Yao; Zheng, Liwei; Fan, Li; Guo, Rui; Lin, Jiong; Wu, Jiahua; Tan, Jiali

doi:10.2174/1574888x11666161129142525

Cited by 10 publications

(10 citation statements)

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“…The morphogenesis of tooth and supporting tissues is regulated by an intricate network of cell–cell signaling during all steps of tooth development, including the placode, bud, cap, bell, and secretory stages [ 1 , 2 , 3 , 4 , 5 ]. The development processes of tooth and supporting tissues have been highly studied in rodents and revealed the molecular details of signaling interactions between epithelium and mesenchyme [ 4 , 5 , 6 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Facilitation of Bone Healing Processes Based on the Developmental Function of Meox2 in Tooth Loss Lesion

Kim

Park

Aryal

et al. 2020

IJMS

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In the present study, we examined the bone healing capacity of Meox2, a homeobox gene that plays essential roles in the differentiation of a range of developing tissues, and identified its putative function in palatogenesis. We applied the knocking down of Meox2 in human periodontal ligament fibroblasts to examine the osteogenic potential of Meox2. Additionally, we applied in vivo periodontitis induced experiment to reveal the possible application of Meox2 knockdown for 1 and 2 weeks in bone healing processes. We examined the detailed histomorphological changes using Masson’s trichrome staining and micro-computed tomography evaluation. Moreover, we observed the localization patterns of various signaling molecules, including α-SMA, CK14, IL-1β, and MPO to examine the altered bone healing processes. Furthermore, we investigated the process of bone formation using immunohistochemistry of Osteocalcin and Runx2. On the basis of the results, we suggest that the knocking down of Meox2 via the activation of osteoblast and modulation of inflammation would be a plausible answer for bone regeneration as a gene therapy. Additionally, we propose that the purpose-dependent selection and application of developmental regulation genes are important for the functional regeneration of specific tissues and organs, where the pathological condition of tooth loss lesion would be.

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Section: Introductionmentioning

confidence: 99%

Facilitation of Bone Healing Processes Based on the Developmental Function of Meox2 in Tooth Loss Lesion

Kim

Park

Aryal

et al. 2020

IJMS

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“…Transcriptional regulation is fundamental to understanding the molecular mechanism of tooth development [31, 32]. However, at present, none of the known lncRNAs have demonstrated functional roles in tooth development in large mammals [33].…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of LncRNA-mRNA Coexpression in the Extracellular Matrix of Developing Deciduous Teeth in Miniature Pigs

Wang

et al. 2019

BioMed Research International

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Miniature pigs, a valuable alternative model for understanding human tooth development, have deciduous teeth from all four tooth families that are replaced once by permanent molars. The extracellular matrix (ECM) supports cells and maintains the integrity of tooth germs during tooth development. However, details on the role of the ECM in tooth development are poorly understood. Here, we performed long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression profiles in the ECM components of deciduous tooth germs by RNA sequencing in miniature pigs. From the early cap to the late bell stages, we identified 4,562 and 3,238 differentially expressed genes (DEGs) from E40 to E50 and E50 to E60, respectively. In addition, a total of 1,464 differentially expressed lncRNAs from E40 to E50 and 969 differentially expressed lncRNAs from E50 to E60 were obtained. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that DEGs were enriched significantly for multiple signaling pathways, especially for the ECM pathway. We then outlined the detailed dynamic gene expression profiling of ECM components during deciduous molar development. Comparison of the cap and bell stages revealed that the structure and functions of the ECM dynamically changed. The ECM-related genes, including THBS1, COL4A5, COL4A6, COL1A1, CHAD, TNR, GP1BA, and ITGA3, were significantly changed, and some were shown to enrich during the bell stage development. Finally, we outlined the coexpression of lncRNAs and ECM properties during tooth development. We showed that the interplay of key lncRNAs could change ECM processes and influence the ECM establishment of tooth patterns to accomplish full tooth formation. These results might provide information to elucidate the regulation network of the lncRNA and ECM in tooth development.

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“…However, every cell in an individual carries the same genetic information encoded in their chromosomes (16). Thus, their exposure to specific signaling molecules are essential to control the cell fate decision, proliferation, and differentiation involved in reparative dentin formation (3,15,17,18).…”

Section: Introductionmentioning

confidence: 99%

“…Epigenetic regulation, such as histone modification (19), is one of the ways to turn gene expression on or off by modifying the chromosome structure without changing the DNA sequence (20). This regulation directs the cells into specific lineages (15,18) and involves two enzyme types, histone acetyltransferases (HATs) and histone deacetylases (HDACs), generating histone acetylation and deacetylation, respectively (19,20). Acetylation by HATs is associated with gene activation through nucleosome relaxation.…”

Section: Introductionmentioning

confidence: 99%

Hydroxamate-Based Histone Deacetylase Inhibitors as Potential Mediators to Induce Dentine Regeneration by Human Dental Pulp Cell

et al. 2021

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Human dental pulp cells (hDPCs) have shown their plasticity when treated with the hydroxamate-based histone deacetylase (HDAC) inhibitor members, Trichostatin A (TSA), and suberoylanilide hydroxamic acid (SAHA). However, a comparison of their potency to stimulate odontoblast-like differentiation and mineralization has not been reported. The aim of our study was to confirm and compare these TSA and SAHA effects. Primary hDPCs cultured with/without various TSA or SAHA concentrations were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), ALP activity, alizarin red staining, and scratch wound healing assays. The inhibitory effect of TSA and SAHA on inhibiting the activity of HDAC was evaluated by HDAC activity assay. Odontoblast-related gene expression was determined using RT-qPCR. The MTT assay indicated that TSA or SAHA did not affect hDPC viability. TSA or SAHA treatment-induced odontoblast-like differentiation as evidenced by a significant increase in alkaline phosphatase activity and mineral deposition after 400 nM TSA or 1 μM SAHA treatment. A significant increase in nuclear factor I C, kruppel like factor 4, dentin matrix acidic phosphoprotein 1, dentin sialophosphoprotein, collagen type I alpha 1 chain, alkaline phosphatase (ALPL), integrin-binding sialoprotein, bone gamma-carboxyglutamate protein, vascular endothelial growth factor A, and cyclin-dependent kinase inhibitor 1A gene expression analyzed by RT-qPCR, at 24, 72 h, 7, and 10 days of treatment. The activity of HDAC in hDPCs culture was significantly inhibited after 72 h TSA and SAHA treatment. The scratch wound healing assay displayed enhanced cell migration at 72 h after TSA or SAHA treatment. Our findings demonstrated that TSA and SAHA have similar stimulatory effects in inducing HDPC odontogenic differentiation and mineralization and propose another potential use of TSA and SAHA to promote dentin regeneration.

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The Epigenetic Regulation in Tooth Development and Regeneration

Cited by 10 publications

References 0 publications

Facilitation of Bone Healing Processes Based on the Developmental Function of Meox2 in Tooth Loss Lesion

Facilitation of Bone Healing Processes Based on the Developmental Function of Meox2 in Tooth Loss Lesion

Integrated Analysis of LncRNA-mRNA Coexpression in the Extracellular Matrix of Developing Deciduous Teeth in Miniature Pigs

Hydroxamate-Based Histone Deacetylase Inhibitors as Potential Mediators to Induce Dentine Regeneration by Human Dental Pulp Cell

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