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International Dental Journal Jun 2023The differentiation of stem cells from exfoliated deciduous teeth (SHEDs) into odontoblasts determines the regeneration of dentin-pulp complex. Non-coding RNAs (ncRNAs),...
BACKGROUND
The differentiation of stem cells from exfoliated deciduous teeth (SHEDs) into odontoblasts determines the regeneration of dentin-pulp complex. Non-coding RNAs (ncRNAs), including microRNA (miRNA) and long non-coding RNA (lncRNA), participate in many multiple biological processes, but the specific miRNAs involved in odontogenesis are incompletely defined. It was confirmed that lncRNA IGFBP7-AS1 could positively regulate odontogenetic differentiation in SHEDs. To investigate the downstream mechanisms of this process, miR-335-3p and miR-155-5p were found to be closely related with SHED odontogenic differentiation through whole-genome sequencing. The aim of the current study was to determine the role of miR-335-3p/miR-155-5p in IGFBP7-AS1-enhanced SHED differentiation and explore the potential mechanism of IGFBP7-AS1-mediated odontogenesis.
METHODS
Putative miR-335-3p/miR-155-5p binding sites within IGFBP7-AS1 were identified by bioinformatics analysis, and the binding of miR-335-3p/miR-155-5p to these sites was confirmed by dual-luciferase reporter gene assays. The effects of miR-335-3p/miR-155-5p in odontogenesis were detected by tissue nonspecific alkaline phosphatase staining, Alizarin red staining, quantitative real-time polymerase chain reaction (qRT-PCR) analyses, and western blot testing. The molecular mechanisms of miR-335-3p/miR-155-5p involved in IGFBP7-AS1-mediated odontogenesis were analysed by qRT-PCR and western blot testing.
RESULTS
Dual-luciferase reporter gene assays showed that miR-335-3p/miR-155-5p could directly bind to IGFBP7-AS1. MiR-335-3p and miR-155-5p both could down-regulate dentin sialophosphoprotein expression, and both miRNAs could inhibit IGFBP7-AS1-mediated SHED odontogenetic differentiation via suppression of the extracellular signal-regulated kinase (ERK) pathway.
CONCLUSIONS
Both miR-335-3p and miR-155-5p were negative regulators to IGFBP7-AS1-enhanced odontogenic differentiation of SHED through suppression of the ERK pathway.
Topics: Humans; RNA, Long Noncoding; MicroRNAs; Cell Differentiation; Odontogenesis; Luciferases
PubMed: 35999071
DOI: 10.1016/j.identj.2022.07.008 -
International Journal of Molecular... Nov 2020Dental enamel is hardest tissue in the body and is produced by dental epithelial cells residing in the tooth. Their cell fates are tightly controlled by transcriptional... (Review)
Review
Dental enamel is hardest tissue in the body and is produced by dental epithelial cells residing in the tooth. Their cell fates are tightly controlled by transcriptional programs that are facilitated by fate determining transcription factors and chromatin regulators. Understanding the transcriptional program controlling dental cell fate is critical for our efforts to build and repair teeth. In this review, we describe the current understanding of these regulators essential for regeneration of dental epithelial stem cells and progeny, which are identified through transgenic mouse models. We first describe the development and morphogenesis of mouse dental epithelium in which different subpopulations of epithelia such as ameloblasts contribute to enamel formation. Then, we describe the function of critical factors in stem cells or progeny to drive enamel lineages. We also show that gene mutations of these factors are associated with dental anomalies in craniofacial diseases in humans. We also describe the function of the master regulators to govern dental lineages, in which the genetic removal of each factor switches dental cell fate to that generating hair. The distinct and related mechanisms responsible for the lineage plasticity are discussed. This knowledge will lead us to develop a potential tool for bioengineering new teeth.
Topics: Ameloblasts; Animals; Cell Differentiation; Epithelial Cells; Epithelium; Gene Expression Regulation; Humans; Mice; Mice, Transgenic; Odontogenesis; Tooth; Transcription, Genetic
PubMed: 33255698
DOI: 10.3390/ijms21238952 -
International Journal of Molecular... Apr 2023Heat shock proteins (HSPs) are a class of molecular chaperones with expression increased in response to heat or other stresses. HSPs regulate cell homeostasis by... (Review)
Review
Heat shock proteins (HSPs) are a class of molecular chaperones with expression increased in response to heat or other stresses. HSPs regulate cell homeostasis by modulating the folding and maturation of intracellular proteins. Tooth development is a complex process that involves many cell activities. During tooth preparation or trauma, teeth can be damaged. The damaged teeth start their repair process by remineralizing and regenerating tissue. During tooth development and injury repair, different HSPs have different expression patterns and play a special role in odontoblast differentiation and ameloblast secretion by mediating signaling pathways or participating in protein transport. This review explores the expression patterns and potential mechanisms of HSPs, particularly HSP25, HSP60 and HSP70, in tooth development and injury repair.
Topics: Heat-Shock Proteins; Molecular Chaperones; HSP70 Heat-Shock Proteins; Odontogenesis; HSP90 Heat-Shock Proteins
PubMed: 37108621
DOI: 10.3390/ijms24087455 -
Journal of Dental Research Oct 2017Tooth is made of an enamel-covered crown and a cementum-covered root. Studies on crown dentin formation have been a major focus in tooth development for several decades.... (Review)
Review
Tooth is made of an enamel-covered crown and a cementum-covered root. Studies on crown dentin formation have been a major focus in tooth development for several decades. Interestingly, the population prevalence for genetic short root anomaly (SRA) with no apparent defects in crown is close to 1.3%. Furthermore, people with SRA itself are predisposed to root resorption during orthodontic treatment. The discovery of the unique role of Nfic (nuclear factor I C; a transcriptional factor) in controlling root but not crown dentin formation points to a new concept: tooth crown and root have different control mechanisms. Further genetic mechanism studies have identified more key molecules (including Osterix, β-catenin, and sonic hedgehog) that play a critical role in root formation. Extensive studies have also revealed the critical role of Hertwig's epithelial root sheath in tooth root formation. In addition, Wnt10a has recently been found to be linked to multirooted tooth furcation formation. These exciting findings not only fill the critical gaps in our understanding about tooth root formation but will aid future research regarding the identifying factors controlling tooth root size and the generation of a whole "bio-tooth" for therapeutic purposes. This review starts with human SRA and mainly focuses on recent progress on the roles of NFIC-dependent and NFIC-independent signaling pathways in tooth root formation. Finally, this review includes a list of the various Cre transgenic mouse lines used to achieve tooth root formation-related gene deletion or overexpression, as well as strengths and limitations of each line.
Topics: Animals; Dental Cementum; Dentin; Enamel Organ; Hedgehog Proteins; Humans; Mice; NFI Transcription Factors; Nerve Tissue Proteins; Odontogenesis; Signal Transduction; Sp7 Transcription Factor; Tooth Root; Transcription Factors; Wnt Proteins; beta Catenin
PubMed: 28665752
DOI: 10.1177/0022034517717478 -
Archives of Oral Biology Aug 2022This review aimed to present an overview of the effect of bone morphogenetic protein 4 (BMP4) on craniofacial and skeletal development, particularly the specific role of... (Review)
Review
OBJECTIVE
This review aimed to present an overview of the effect of bone morphogenetic protein 4 (BMP4) on craniofacial and skeletal development, particularly the specific role of BMP4 in tooth development.
DESIGN
The search for this narrative review was conducted in PubMed, Web of Science, Embase, and ScienceDirect using relevant keywords, including checking reference lists of journal articles by hand searching.
RESULTS
Mutations or deletions of BMP4 cause tissue development defects in mice and humans, such as fragile bone, craniofacial deformity, cleft lip and palate, tooth development stagnation, and abnormal structure.
CONCLUSIONS
BMP4 is a reliable and vital candidate to regulate the development of bones, craniofacies, and teeth. It also has high clinical application potential.
Topics: Animals; Bone Morphogenetic Protein 4; Cleft Lip; Cleft Palate; Mice; Odontogenesis; Tooth
PubMed: 35662681
DOI: 10.1016/j.archoralbio.2022.105465 -
Archives of Oral Biology Jan 2018Homeobox genes are a group of conserved class of transcription factors that function as key regulators during the embryonic developmental processes. They act as master... (Review)
Review
OBJECTIVES
Homeobox genes are a group of conserved class of transcription factors that function as key regulators during the embryonic developmental processes. They act as master regulator for developmental genes, which involves coordinated actions of various auto and cross-regulatory mechanisms. In this review, we summarize the expression pattern of homeobox genes in relation to the tooth development and various signaling pathways or molecules contributing to the specific actions of these genes in the regulation of odontogenesis.
MATERIALS AND METHODS
An electronic search was undertaken using combination of keywords e.g. Homeobox genes, tooth development, dental diseases, stem cells, induced pluripotent stem cells, gene control region was used as search terms in PubMed and Web of Science and relevant full text articles and abstract were retrieved that were written in English. A manual hand search in text books were also carried out. Articles related to homeobox genes in dentistry and tissue engineering and regenerative medicine of odontogenesis were selected.
RESULTS
The possible perspective of stem cells technology in odontogenesis and subsequent analysis of gene correction pertaining to dental disorders through the possibility of induced pluripotent stem cells technology is also inferred.
CONCLUSIONS
We demonstrate the promising role of tissue engineering and regenerative medicine on odontogenesis, which can generate a new ray of hope in the field of dental science.
Topics: Animals; Genes, Homeobox; Humans; Odontogenesis; Regenerative Medicine; Stem Cells
PubMed: 29031235
DOI: 10.1016/j.archoralbio.2017.09.033 -
Journal of Oral Biosciences Mar 2021Odontogenic tumors, derived from epithelial, ectomesenchymal, and/or mesenchymal elements of the tooth-forming apparatus, constitute a heterogeneous group of lesions,... (Review)
Review
BACKGROUND
Odontogenic tumors, derived from epithelial, ectomesenchymal, and/or mesenchymal elements of the tooth-forming apparatus, constitute a heterogeneous group of lesions, including hamartomas, benign and malignant neoplasms with metastatic capabilities.
HIGHLIGHT
This review provides a comprehensive overviewof the pathogenesis of odontogenic tumors and explains the associated molecular events in the context of hallmarks of cancer established by Hanahan D and Weinberg RA. Diagrammatic representations depicted in the article would facilitate easier understanding.
CONCLUSION
A better understanding of the pathogenesis of the lesions may assist in determining patient's prognosis and devising better targeted therapeutic treatment, thus, reducing the morbidity and mortalityof patients.
Topics: Ameloblastoma; Hamartoma; Humans; Odontogenesis; Odontogenic Tumors; Prognosis
PubMed: 33476705
DOI: 10.1016/j.job.2020.12.001 -
Oral Surgery, Oral Medicine, Oral... Mar 2019Odontogenic tumors bear some histopathologic and molecular resemblance to craniopharyngiomas. Specifically, adamantinomatous craniopharyngioma shares morphologic... (Review)
Review
Odontogenic tumors bear some histopathologic and molecular resemblance to craniopharyngiomas. Specifically, adamantinomatous craniopharyngioma shares morphologic features and CTNNB1 (the gene encoding β-catenin) mutations with calcifying odontogenic cyst, whereas papillary craniopharyngioma and ameloblastoma are driven by BRAF mutations. Recently, important similarities between adamantinomatous craniopharyngioma and the cell signaling pathways involved in tooth formation have been described. Here, we expand the interpretation of these data in the context of odontogenic tumors. We discuss some morphologic and molecular features that are shared by tumors from these 2 distinct sites (i.e., craniopharyngiomas and odontogenic tumors). Current conservative surgical treatment is effective in most cases of benign odontogenic tumors, but in the future, the understanding of the molecular pathogenesis could impact the treatment of aggressive and/or malignant cases.
Topics: Craniopharyngioma; Humans; Mutation; Odontogenesis; Odontogenic Tumors; Pituitary Neoplasms
PubMed: 30598409
DOI: 10.1016/j.oooo.2018.11.004 -
Annals of African Medicine 2017Resorptive cells are responsible for the resorption of mineralized matrix of hard tissues. Bone-resorbing cells are called osteoclasts; however, they can resorb... (Review)
Review
Resorptive cells are responsible for the resorption of mineralized matrix of hard tissues. Bone-resorbing cells are called osteoclasts; however, they can resorb mineralized dental tissues or calcified cartilage and then they are called odontoclasts and chondroclasts, respectively. Resorptive cells form when mononuclear precursors derived from a monocyte-macrophage cell lineage are attracted to certain mineralized surfaces and subsequently fuse and adhere onto them for exerting their resorbing activity. These cells are responsible for degradation of calcified extracellular matrix composed of organic molecules and hydroxyapatite. The activity of these cells can be observed in both physiological and pathological processes throughout life and their activity is mainly required in bone turnover and growth, spontaneous and induced (orthodontic) tooth movement, tooth eruption, and bone fracture healing, as well as in pathological conditions such as osteoporosis, osteoarthritis, and bone metastasis. In addition, they are responsible for daily control of calcium homeostasis. Clastic cells also resorb the primary teeth for shedding before the permanent teeth erupt into the oral cavity.
Topics: Bone Diseases; Bone Resorption; Calcification, Physiologic; Humans; Odontogenesis; Osteoclasts; Tooth, Deciduous
PubMed: 28469115
DOI: 10.4103/aam.aam_97_16 -
Current Stem Cell Research & Therapy 2018Tooth root development begins after the completion of tooth crown development. Both the tooth root and crown undergo a series of interactions between the epithelium and... (Review)
Review
BACKGROUND
Tooth root development begins after the completion of tooth crown development. Both the tooth root and crown undergo a series of interactions between the epithelium and adjacent mesenchymal cells. Although many studies have evaluated tooth crown formation, little is known about the regulatory mechanisms of tooth root development. MicroRNAs (miRNAs) are small noncoding RNAs that regulate protein expression through post-transcriptional mechanisms and participate in a broad range of biological processes, from development to tumorigenesis. The functional importance of miRNAs on the development of tooth root and periodontal tissues has been suggested in many studies.
OBJECTIVE
To summarize the functions of miRNAs on tooth root and periodontal tissue development.
RESULTS
MicroRNAs are important to root odontogenesis, Hertwig's epithelial root sheath and periodontal tissue development, and have functions in stem cells from dental or periodontal tissues.
CONCLUSION
The modulation of miRNAs in tooth root and periodontal tissue development is fine tuning.
Topics: Animals; Epithelial Cells; Humans; Mesenchymal Stem Cells; MicroRNAs; Odontogenesis; Tooth; Tooth Root
PubMed: 28707582
DOI: 10.2174/1574888X12666170713123647