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World Journal of Stem Cells Nov 2021Dental stem cells can differentiate into different types of cells. Dental pulp stem cells, stem cells from human exfoliated deciduous teeth, periodontal ligament stem... (Review)
Review
Dental stem cells can differentiate into different types of cells. Dental pulp stem cells, stem cells from human exfoliated deciduous teeth, periodontal ligament stem cells, stem cells from apical papilla, and dental follicle progenitor cells are five different types of dental stem cells that have been identified during different stages of tooth development. The availability of dental stem cells from discarded or removed teeth makes them promising candidates for tissue engineering. In recent years, three-dimensional (3D) tissue scaffolds have been used to reconstruct and restore different anatomical defects. With rapid advances in 3D tissue engineering, dental stem cells have been used in the regeneration of 3D engineered tissue. This review presents an overview of different types of dental stem cells used in 3D tissue regeneration, which are currently the most common type of stem cells used to treat human tissue conditions.
PubMed: 34909114
DOI: 10.4252/wjsc.v13.i11.1610 -
International Journal of Molecular... Jan 2023Oligodontia manifests as a congenital reduction in the number of permanent teeth. Despite the major efforts that have been made, the genetic etiology of oligodontia...
Oligodontia manifests as a congenital reduction in the number of permanent teeth. Despite the major efforts that have been made, the genetic etiology of oligodontia remains largely unknown. Bone morphogenetic protein receptor type 2 (BMPR2) variants have been associated with pulmonary arterial hypertension (PAH). However, the genetic significance of BMPR2 in oligodontia has not been previously reported. In the present study, we identified a novel heterozygous variant (c.814C > T; p.Arg272Cys) of BMPR2 in a family with nonsyndromic oligodontia by performing whole-exome sequencing. In addition, we identified two additional heterozygous variants (c.1042G > A; p.Val348Ile and c.1429A > G; p.Lys477Glu) among a cohort of 130 unrelated individuals with nonsyndromic oligodontia by performing Sanger sequencing. Functional analysis demonstrated that the activities of phospho-SMAD1/5/8 were significantly inhibited in BMPR2-knockout 293T cells transfected with variant-expressing plasmids, and were significantly lower in BMPR2 heterozygosity simulation groups than in the wild-type group, indicating that haploinsufficiency may represent the genetic mechanism. RNAscope in situ hybridization revealed that BMPR2 transcripts were highly expressed in the dental papilla and adjacent inner enamel epithelium in mice tooth germs, suggesting that BMPR2 may play important roles in tooth development. Our findings broaden the genetic spectrum of oligodontia and provide clinical and genetic evidence supporting the importance of BMPR2 in nonsyndromic oligodontia.
Topics: Animals; Mice; Anodontia; Bone Morphogenetic Protein Receptors, Type II; Mutation; Humans
PubMed: 36675162
DOI: 10.3390/ijms24021648 -
European Review For Medical and... Jul 2019The aim of this study was to investigate the effect of melatonin on mitochondria of dental papilla cells (DPCs) during the odontogenic differentiation process.
OBJECTIVE
The aim of this study was to investigate the effect of melatonin on mitochondria of dental papilla cells (DPCs) during the odontogenic differentiation process.
MATERIALS AND METHODS
Primary DPCs were obtained from the first molar dental papilla of neonatal rats and cultured in osteogenic (OS) or basal medium supplemented with melatonin at different concentrations (0, 1 pM, 0.1 nM, 10 nM, and 1 μM) for differentiation in vitro. Effects of melatonin on differentiation, mitochondrial respiratory function, and mitochondrial biogenesis of DPCs were analyzed.
RESULTS
Upon odontogenic induction, Alkaline phosphatase (ALP) activity, dentin sialophosphoprotein (DSPP), and dentin matrix protein (DMP1) expression were significantly enhanced, with a peaked expression at 10 nM of melatonin treatment. During DPCs differentiation, 10 nM melatonin could significantly induce the increase of intracellular Adenosine triphosphate (ATP), the decrease of the oxidized form of nicotinamide adenine dinucleotide (NAD+)/NADH ratio and reactive oxygen species (ROS). The mRNA and protein levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1), and mitochondrial transcription factor A (TFAM) were significantly increased, and the peak level of expression was found in cells treated with 10 nM of melatonin. Furthermore, the mitochondria DNA (mtDNA) copy number was significantly decreased during DPCs differentiation.
CONCLUSIONS
These findings suggest that melatonin can promote the differentiation of rat DPCs and regulate mitochondrial energy metabolism, ROS scavenging, and mitochondrial biogenesis.
Topics: Animals; Cell Differentiation; Cells, Cultured; Dental Papilla; Dose-Response Relationship, Drug; Melatonin; Mitochondria; Organelle Biogenesis; Rats; Rats, Sprague-Dawley
PubMed: 31298348
DOI: 10.26355/eurrev_201907_18343 -
International Journal of Oral Science Mar 2009Tooth loss compromises human oral health. Although several prosthetic methods, such as artificial denture and dental implants, are clinical therapies to tooth loss... (Review)
Review
Tooth loss compromises human oral health. Although several prosthetic methods, such as artificial denture and dental implants, are clinical therapies to tooth loss problems, they are thought to have safety and usage time issues. Recently, tooth tissue engineering has attracted more and more attention. Stem cell based tissue engineering is thought to be a promising way to replace the missing tooth. Mesenchymal stem cells (MSCs) are multipotent stem cells which can differentiate into a variety of cell types. The potential MSCs for tooth regeneration mainly include stem cells from human exfoliated deciduous teeth (SHEDs), adult dental pulp stem cells (DPSCs), stem cells from the apical part of the papilla (SCAPs), stem cells from the dental follicle (DFSCs), periodontal ligament stem cells (PDLSCs) and bone marrow derived mesenchymal stem cells (BMSCs). This review outlines the recent progress in the mesenchymal stem cells used in tooth regeneration.
Topics: Adult Stem Cells; Bone Marrow Cells; Dental Papilla; Dental Pulp; Dental Sac; Humans; Mesenchymal Stem Cells; Multipotent Stem Cells; Periodontal Ligament; Regeneration; Tissue Engineering; Tooth; Tooth, Deciduous
PubMed: 20690498
DOI: 10.4248/ijos.08032 -
Annals of Medicine Dec 2017Since the disclosure of adult mesenchymal stem cells (MSCs), there have been an intense investigation on the characteristics of these cells and their potentialities.... (Review)
Review
Since the disclosure of adult mesenchymal stem cells (MSCs), there have been an intense investigation on the characteristics of these cells and their potentialities. Dental stem cells (DSCs) are MSC-like populations with self-renewal capacity and multidifferentiation potential. Currently, there are five main DSCs, dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP), periodontal ligament stem cells (PDLSCs) and dental follicle precursor cells (DFPCs). These cells are extremely accessible, prevail during all life and own an amazing multipotency. In the past decade, DPSCs and SHED have been thoroughly studied in regenerative medicine and tissue engineering as autologous stem cells therapies and have shown amazing therapeutic abilities in oro-facial, neurologic, corneal, cardiovascular, hepatic, diabetic, renal, muscular dystrophy and auto-immune conditions, in both animal and human models, and most recently some of them in human clinical trials. In this review, we focus the characteristics, the multiple roles of DSCs and its potential translation to clinical settings. These new insights of the apparently regenerative aptitude of these DSCs seems quite promising to investigate these cells abilities in a wide variety of pathologies. Key messages Dental stem cells (DSCs) have a remarkable self-renewal capacity and multidifferentiation potential; DSCs are extremely accessible and prevail during all life; DSCs, as stem cells therapies, have shown amazing therapeutic abilities in oro-facial, neurologic, corneal, cardiovascular, hepatic, diabetic, renal, muscular dystrophy and autoimmune conditions; DSCs are becoming extremely relevant in tissue engineering and regenerative medicine.
Topics: Adult; Dental Papilla; Dental Pulp; Dental Sac; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Periodontal Ligament; Regenerative Medicine; Tissue Engineering; Tooth; Tooth, Deciduous
PubMed: 28649865
DOI: 10.1080/07853890.2017.1347705 -
Journal of Pharmacy & Bioallied Sciences Aug 2020Diabetes mellitus is an endocrinal disorder affecting worldwide and the disease incidence is rising alarmingly high. The effects of diabetes on tooth development are... (Review)
Review
Diabetes mellitus is an endocrinal disorder affecting worldwide and the disease incidence is rising alarmingly high. The effects of diabetes on tooth development are explored by limited studies and their molecular insights are very rarely studied. This systematic review is aimed to provide the best scientific literature source on the molecular insights into odontogenesis in hyperglycemic environment caused by diabetes mellitus or by maternal diabetes on the offspring. The literature search was conducted on the databases, namely PubMed, PubMed Central, Cochrane, and Scopus. The original studies exploring the alterations in the molecular pathways of odontogenesis in diabetes mellitus were selected. Data were extracted, chosen, and evaluated by two independent researchers. At the end of thorough data search, four articles were eligible for the review. Three articles brought out the molecular pathways involved in the offspring of gestational diabetes through animal models. Fourth article was an study, which treated the stem cells in hyperglycemic environment and drafted the molecular pathway. The altered molecular pathways in dental epithelial stem cells (DESCs), dental papilla cells (DPCs), and stem cells from apical papilla were studied and empowered with statistical analysis. Thus with this systematic review, we conclude that apurinic/apyrimidinic endonuclease1 downregulation causing deoxyribonucleic acid hypermethylation and gene silencing, activation of toll-like receptor-4/nuclear factor kappa B (TLR4/NF-κB) pathway are involved in suppressing cell proliferation and accelerated apoptosis in DESCs in high glucose environment. DPCs are suppressed from odonto differentiation by activation of TLR4 signaling and resulting inhibition of SMAD1/5/9 phosphorylation in diabetic condition. NF-κB pathway activation causes decreased cell proliferation and enhanced differentiation in apical papilla stem cells in hyperglycemia. Further studies targeting various stages of odontogenesis can reveal more molecular insight.
PubMed: 33149430
DOI: 10.4103/jpbs.JPBS_159_20 -
Frontiers in Physiology 2021circular RNAs (circRNAs) is a broad and diverse endogenous subfamily of non-coding RNAs, regulating the gene expression by acting as a microRNA (miRNA) sponge. However,...
circular RNAs (circRNAs) is a broad and diverse endogenous subfamily of non-coding RNAs, regulating the gene expression by acting as a microRNA (miRNA) sponge. However, the biological functions of circRNAs in odontoblast differentiation remain largely unknown. Our preliminary study identified an unknown mouse circRNA by circRNA sequencing generated from mouse dental papilla and we termed it circKLF4. In this study, quantitative real-time PCR and hybridization were used and demonstrated that circKLF4 was upregulated during odontoblastic differentiation. Gene knockdown and overexpression assays indicated that circKLF4 promoted odontoblastic differentiation of mouse dental papilla cells (mDPCs). Mechanistically, we found that circKLF4 increased the linear KLF4 expression in a microRNA-dependent manner. By mutating the binding sites of microRNA and circKLF4, we further confirmed that circKLF4 acted as sponge of miRNA-1895 and miRNA-5046 to promote the expression of KLF4. We then also found that ENDOGLIN was also up-regulated by circKLF4 by transfection of circKLF4 overexpression plasmids with or without microRNA inhibitor. In conclusion, circKLF4 increases the expression of KLF4 and ENDOGLIN to promote odontoblastic differentiation sponging miRNA-1895 and miRNA-5046.
PubMed: 35222058
DOI: 10.3389/fphys.2021.760223 -
Journal of Indian Society of... 2022The regeneration and maintenance of the interdental papilla presents a great challenge to the clinician while smile designing. Proportions of papilla height (PH),...
BACKGROUND
The regeneration and maintenance of the interdental papilla presents a great challenge to the clinician while smile designing. Proportions of papilla height (PH), crestal PH (CPH), and proximal contact areas (PCA) are more stable parameters.
AIM
The purpose of the present study was to evaluate and correlate the papilla proportion (PP), crestal PP (CPP), and PCA proportion (PCAP) in periodontally healthy males and females.
MATERIALS AND METHODS
One hundred and twenty patients in an age group of 20-40 years, divided equally based on gender, were assessed for PH, CPH, and PCA of maxillary anterior teeth. The findings were recorded on study models and radiographs to obtain the PP, CPP, and PCAP on the mesial and distal aspects of respective tooth.
STATISTICAL ANALYSIS
The overall comparison of parameters was performed using paired -test.
RESULTS
The mean mesial PP (43.51% ± 3.10% for male and 45.23% ± 2.23% for female) and CPP values (48.36% ± 3.35% for male and 51.16% ± 2.96% for female) were found to be greater of each tooth type and were more pronounced for females. The PCAP values were greater for distal aspects (36.76% ± 7.00% for males and 33.30% ± 6.93% for females).
CONCLUSION
The results of the study indicate that PP and CPP are more pronounced in females, while the PCAP is more marked in males. Furthermore, it appears that the PP and CPP are inversely related to the PCAP in both males and females.
PubMed: 36339384
DOI: 10.4103/jisp.jisp_251_21 -
Brazilian Dental Journal 2011In recent years, stem cell research has grown exponentially owing to the recognition that stem cell-based therapies have the potential to improve the life of patients... (Review)
Review
In recent years, stem cell research has grown exponentially owing to the recognition that stem cell-based therapies have the potential to improve the life of patients with conditions that range from Alzheimer's disease to cardiac ischemia and regenerative medicine, like bone or tooth loss. Based on their ability to rescue and/or repair injured tissue and partially restore organ function, multiple types of stem/progenitor cells have been speculated. Growing evidence demonstrates that stem cells are primarily found in niches and that certain tissues contain more stem cells than others. Among these tissues, the dental tissues are considered a rich source of mesenchymal stem cells that are suitable for tissue engineering applications. It is known that these stem cells have the potential to differentiate into several cell types, including odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. In dentistry, stem cell biology and tissue engineering are of great interest since may provide an innovative for generation of clinical material and/or tissue regeneration. Mesenchymal stem cells were demonstrated in dental tissues, including dental pulp, periodontal ligament, dental papilla, and dental follicle. These stem cells can be isolated and grown under defined tissue culture conditions, and are potential cells for use in tissue engineering, including, dental tissue, nerves and bone regeneration. More recently, another source of stem cell has been successfully generated from human somatic cells into a pluripotent stage, the induced pluripotent stem cells (iPS cells), allowing creation of patient- and disease-specific stem cells. Collectively, the multipotency, high proliferation rates, and accessibility make the dental stem cell an attractive source of mesenchymal stem cells for tissue regeneration. This review describes new findings in the field of dental stem cell research and on their potential use in the tissue regeneration.
Topics: Animals; Cell Differentiation; Dental Papilla; Dental Pulp; Dental Sac; Humans; Induced Pluripotent Stem Cells; Mesenchymal Stem Cells; Molar, Third; Periodontal Ligament; Regeneration; Tissue Engineering; Tooth Apex; Tooth Exfoliation; Tooth, Deciduous
PubMed: 21537580
DOI: 10.1590/s0103-64402011000200001 -
Frontiers in Genetics 2021Bmp2 is essential for dentin development and formation. Bmp2 conditional knock-out (KO) mice display a similar tooth phenotype of dentinogenesis imperfecta (DGI). To...
Bmp2 is essential for dentin development and formation. Bmp2 conditional knock-out (KO) mice display a similar tooth phenotype of dentinogenesis imperfecta (DGI). To elucidate a foundation for subsequent functional studies of cross talk between mRNAs and lncRNAs in Bmp2-mediated dentinogenesis, we investigated the profiling of lncRNAs and mRNAs using immortalized mouse dental Bmp2 flox/flox (iBmp2) and Bmp2 knock-out (iBmp2) papilla cells. RNA sequencing was implemented to study the expression of the lncRNAs and mRNAs. Quantitative real-time PCR (RT-qPCR) was used to validate expressions of lncRNAs and mRNAs. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to predict functions of differentially expressed genes (DEGs). Protein-protein interaction (PPI) and lncRNA-mRNA co-expression network were analyzed by using bioinformatics methods. As a result, a total of 22 differentially expressed lncRNAs (16 downregulated vs 6 upregulated) and 227 differentially expressed mRNAs (133 downregulated vs. 94 upregulated) were identified in the iBmp2 cells compared with those of the iBmp2 cells. RT-qPCR results showed significantly differential expressions of several lncRNAs and mRNAs which were consistent with the RNA-seq data. GO and KEGG analyses showed differentially expressed genes were closely related to cell differentiation, transcriptional regulation, and developmentally relevant signaling pathways. Moreover, network-based bioinformatics analysis depicted the co-expression network between lncRNAs and mRNAs regulated by Bmp2 in mouse dental papilla cells and symmetrically analyzed the effect of Bmp2 during dentinogenesis via coding and non-coding RNA signaling.
PubMed: 35003201
DOI: 10.3389/fgene.2021.702540