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International Journal of Molecular... Jun 2023Stem cells from the apical papilla (SCAPs) are used to regulate the microenvironment of nerve defects. KDM6B, which functions as an H3K27me3 demethylase, is known to...
Stem cells from the apical papilla (SCAPs) are used to regulate the microenvironment of nerve defects. KDM6B, which functions as an H3K27me3 demethylase, is known to play a crucial role in neurogenesis. However, the mechanism by which KDM6B influences the neurogenesis potential of SCAPs remains unclear. We evaluated the expression of neural markers in SCAPs by using real-time RT-PCR and immunofluorescence staining. To assess the effectiveness of SCAP transplantation in the SCI model, we used the BBB scale to evaluate motor function. Additionally, toluidine blue staining and Immunofluorescence staining of NCAM, NEFM, β-III-tubulin, and Nestin were used to assess nerve tissue remodeling. Further analysis was conducted through Microarray analysis and ChIP assay to study the molecular mechanisms. Our results show that KDM6B inhibits the expression of NeuroD, TH, β-III tubulin, and Nestin. In vivo studies indicate that the SCAP-KDM6Bsh group is highly effective in restoring spinal cord structure and motor function in rats suffering from SCI. Our findings suggest that KDM6B directly binds to the HES1 promoter via regulating H3K27me3 and HES1 expression. In conclusion, our study can help understand the regulatory role of KDM6B in neurogenesis and provide more effective treatments for nerve injury.
Topics: Rats; Animals; Histones; Nestin; Cell Differentiation; Tubulin; Stem Cells; Neurogenesis; Dental Papilla; Cells, Cultured; Osteogenesis
PubMed: 37445785
DOI: 10.3390/ijms241310608 -
Biomedicines Jul 2023Dental diseases occurring on young permanent teeth usually lead to the premature arrest of tooth root development. Sustained tooth root elongation is necessary to... (Review)
Review
Dental diseases occurring on young permanent teeth usually lead to the premature arrest of tooth root development. Sustained tooth root elongation is necessary to achieve the goal of long-term preservation of affected teeth. To this end, stem cell-based regenerative endodontic treatment has been regarded as one of the most promising strategies for treating young permanent teeth with pulp and periapical infections. Endogenous stem cells residing in the apical papilla, named stem cells from the apical papilla (SCAPs), have been intensively investigated due to their critical roles in pulp regeneration and root redevelopment. The present review summarizes advances in the field of SCAPs studies and discusses the challenges that need to be further addressed.
PubMed: 37509686
DOI: 10.3390/biomedicines11072047 -
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 -
Clinical Oral Implants Research Sep 2023The aim of this study was to assess the following PIO question: In adult patients treated with an indication for single tooth extraction in the maxillary esthetic zone... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The aim of this study was to assess the following PIO question: In adult patients treated with an indication for single tooth extraction in the maxillary esthetic zone (15-25), what is the influence of an immediate implant placement and immediate loading protocol on the clinical performance (primary aim) and esthetic outcomes (secondary aim) focusing on investigations published after 2010.
MATERIAL AND METHODS
An electronic search in Medline (PubMed), the Cochrane Central Register of Controlled Trials, and EMBASE databases up to April 2022 was performed to identify clinical studies investigating the outcome of single implants subjected to immediate placement with immediate restoration/loading (Type 1A).
RESULTS
Sixty-three studies (10 randomized controlled trials, 28 prospective and 25 retrospective cohort studies) were included with a follow-up ranging from 12 to 96 months. One thousand nine hundred sixty-one implants reported survival rates of 99.2 (98.6-99.5) % at 1 year, 97.5 (95.9-98.4) % after 3 years, and 95.8 (93.3-97.4) % after 5 years; 1064 immediately loaded restorations presented survival rates of 98.9 (97.8-99.5) % after 1 year, 96.8 (93.6-98.4) % after 2 years, and 94.8 (89.6-97.4) % after 5 years. Comparing baseline to 12-month data using the Hedges' g effect size (95% CI), papilla height presented an overall effect size of -0.71 (-1.25, -0.1) mm, midfacial recession change of -0.15 (-0.66, 0.36) mm, and a 0.82 (0.37, 1.28) gain in PES.
CONCLUSIONS
Immediate implant placement and immediate loading can be considered a predictable and safe treatment option for single maxillary anterior restorations with adequate survival rates and favorable esthetics outcomes for up to 5 years.
Topics: Adult; Humans; Prospective Studies; Retrospective Studies; Dental Implants; Esthetics, Dental; Databases, Factual
PubMed: 37750531
DOI: 10.1111/clr.14172 -
Biomedicines Mar 2024Spinal cord injury (SCI), a prevalent and disabling neurological condition, prompts a growing interest in stem cell therapy as a promising avenue for treatment.... (Review)
Review
Spinal cord injury (SCI), a prevalent and disabling neurological condition, prompts a growing interest in stem cell therapy as a promising avenue for treatment. Dental-derived stem cells, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), stem cells from the apical papilla (SCAP), dental follicle stem cells (DFSCs), are of interest due to their accessibility, minimally invasive extraction, and robust differentiating capabilities. Research indicates their potential to differentiate into neural cells and promote SCI repair in animal models at both tissue and functional levels. This review explores the potential applications of dental-derived stem cells in SCI neural repair, covering stem cell transplantation, conditioned culture medium injection, bioengineered delivery systems, exosomes, extracellular vesicle treatments, and combined therapies. Assessing the clinical effectiveness of dental-derived stem cells in the treatment of SCI, further research is necessary. This includes investigating potential biological mechanisms and conducting Large-animal studies and clinical trials. It is also important to undertake more comprehensive comparisons, optimize the selection of dental-derived stem cell types, and implement a functionalized delivery system. These efforts will enhance the therapeutic potential of dental-derived stem cells for repairing SCI.
PubMed: 38540295
DOI: 10.3390/biomedicines12030683 -
International Journal of Oral Science Apr 2022Multiple signaling pathways are involved in the regulation of cell proliferation and differentiation in odontogenesis and dental tissue renewal, but the details of these...
Multiple signaling pathways are involved in the regulation of cell proliferation and differentiation in odontogenesis and dental tissue renewal, but the details of these mechanisms remain unknown. Here, we investigated the expression patterns of a transcription factor, Krüppel-like factor 6 (KLF6), during the development of murine tooth germ and its function in odontoblastic differentiation. KLF6 was almost ubiquitously expressed in odontoblasts at various stages, and it was co-expressed with P21 (to varying degrees) in mouse dental germ. To determine the function of Klf6, overexpression and knockdown experiments were performed in a mouse dental papilla cell line (iMDP-3). Klf6 functioned as a promoter of odontoblastic differentiation and inhibited the proliferation and cell cycle progression of iMDP-3 through p21 upregulation. Dual-luciferase reporter assay and chromatin immunoprecipitation showed that Klf6 directly activates p21 transcription. Additionally, the in vivo study showed that KLF6 and P21 were also co-expressed in odontoblasts around the reparative dentin. In conclusion, Klf6 regulates the transcriptional activity of p21, thus promoting the cell proliferation to odontoblastic differentiation transition in vitro. This study provides a theoretical basis for odontoblast differentiation and the formation of reparative dentine regeneration.
Topics: Animals; Cell Differentiation; Cell Proliferation; Mice; Odontoblasts; Odontogenesis; Tooth Germ
PubMed: 35422483
DOI: 10.1038/s41368-022-00172-6 -
Periodontology 2000 Feb 2024Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with the ability to communicate with other tissues and cell types over long... (Review)
Review
Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with the ability to communicate with other tissues and cell types over long distances. Their use in regenerative medicine has gained tremendous momentum recently due to their ability to be utilized as therapeutic options for a wide array of various diseases. Over 5000 publications are currently being published on this topic yearly, many of which in the dental space. This extensive review article is the first scoping review aimed at summarizing all therapeutic uses of exosomes in regenerative dentistry. A total of 944 articles were identified as using exosomes in the dental field for either their regenerative/therapeutic potential or for diagnostic purposes derived from the oral cavity. In total, 113 research articles were selected for their regenerative potential (102 in vitro, 60 in vivo, 50 studies included both). Therapeutic exosomes were most commonly derived from dental pulps, periodontal ligament cells, gingival fibroblasts, stem cells from exfoliated deciduous teeth, and the apical papilla which have all been shown to facilitate the regenerative potential of a number of tissues including bone, cementum, the periodontal ligament, nerves, aid in orthodontic tooth movement, and relieve temporomandibular joint disorders, among others. Results demonstrate that the use of exosomes led to positive outcomes in 100% of studies. In the bone field, exosomes were found to perform equally as well or better than rhBMP2 while significantly reducing inflammation. Periodontitis animal models were treated with simple gingival injections of exosomes and benefits were even observed when the exosomes were administered intravenously. Exosomes are much more stable than growth factors and were shown to be far more resistant against degradation by periodontal pathogens found routinely in a periodontitis environment. Comparative studies in the field of periodontal regeneration found better outcomes for exosomes even when compared to their native parent stem cells. In total 47 diagnostic studies revealed a role for salivary/crevicular fluid exosomes for the diagnosis of birth defects, cardiovascular disease, diabetes, gingival recession detection, gingivitis, irritable bowel syndrome, neurodegenerative disease, oral lichen planus, oral squamous cell carcinoma, oropharyngeal cancer detection, orthodontic root resorption, pancreatic cancer, periodontitis, peri-implantitis, Sjögren syndrome, and various systemic diseases. Hence, we characterize the exosomes as possessing "remarkable" potential, serving as a valuable tool for clinicians with significant advantages.
Topics: Exosomes; Humans; Regenerative Medicine; Dentistry; Regeneration; Animals
PubMed: 38546137
DOI: 10.1111/prd.12557 -
Archives of Oral Biology Jun 2022Considering the variety of pharmacological activities and the potential to mediate biomineralization, the flavonoids taxifolin and epigallocatechin-3-gallate (EGCG)...
OBJECTIVE
Considering the variety of pharmacological activities and the potential to mediate biomineralization, the flavonoids taxifolin and epigallocatechin-3-gallate (EGCG) could be explored as biomolecules in scaffolds for regenerative endodontic procedures. The aim of this study was to evaluate the effect of taxifolin and EGCG on the cell viability, differentiation, and expression of biomineralization markers in stem cells from the apical papilla.
DESIGN
Stem cells from the apical papilla were exposed to single or continuous treatments with taxifolin at 200, 100 and 50 µM and EGCG at 50, 25 and 12.5 µM for 48 h, 8 and 14 days, in regular or mineralizing media. Cell viability, alkaline phosphatase activity and calcium deposition were analyzed using resazurin, p-nitrophenylphosphate and alizarin-based assays.
RESULTS
None of the flavonoid groups affected cell viability at 48 h, however at 8 and 14 days, Taxifolin 200 µM and EGCG 50 µM were cytotoxic. Cells did not express alkaline phosphatase activity when grown in regular medium, even in the presence of flavonoids. Alkaline phosphatase activity and biomineralization potential were higher in cells treated with Taxifolin 50 µM and EGCG 12.5 µM.
CONCLUSION
Taxifolin and EGCG exhibited a concentration, time, and therapeutic mode dependent bioactivity on stem cells from the apical papilla. Both flavonoids at the lower concentrations tested exhibited cytocompatibility and increased expression of mineralization markers in the presence of mineralizing agents.
Topics: Alkaline Phosphatase; Biomineralization; Catechin; Cell Differentiation; Cells, Cultured; Dental Papilla; Quercetin; Stem Cells
PubMed: 35367790
DOI: 10.1016/j.archoralbio.2022.105413 -
BMC Oral Health Aug 2016Aim of this single center cross-sectional study was to investigate oral behavior, dental, periodontal and microbiological findings in patients undergoing hemodialysis...
BACKGROUND
Aim of this single center cross-sectional study was to investigate oral behavior, dental, periodontal and microbiological findings in patients undergoing hemodialysis (HD) and after kidney transplantation (KT).
METHODS
Patients undergoing HD for end-stage renal failure and after KT were investigated. Oral health behavior was recorded using a standardized questionnaire, e.g. dental behavior, tooth brushing, oral hygiene aids. Oral investigation included screening of oral mucosa, dental findings (DMF-T) and periodontal situation (Papilla bleeding index [PBI] periodontal probing depth [PPD] and clinical attachment loss [CAL]). Additionally, microbiological analysis of subgingival biofilm samples (PCR) was performed.
STATISTICAL ANALYSIS
Student's t-test or Mann-Whitney-U-test, Fisher's exact test (α = 5 %).
RESULTS
A total of 70 patients (HD: n = 35, KT: n = 35) with a mean age of 56.4 ± 11.1 (HD) and 55.8 ± 10.9 (KT) years were included. Lack in use of additional oral hygiene (dental floss, inter-dental brush) was found. KT group presented significantly more gingivial overgrowth (p = 0.01). DMF-T was 19.47 ± 5.84 (HD) and 17.61 ± 5.81 (KT; p = 0.21). Majority of patients had clinically moderate and severe periodontitis; showing a need for periodontal treatment of 57 % (HD) and 71 % (KT; p = 0.30). Significantly higher prevalence of Parvimonas micra and Capnocytophaga species in the HD group were found (p < 0.01).
CONCLUSION
Periodontal treatment need and lack in oral behavior for both groups indicate the necessity of an improved early treatment and prevention of dental and periodontal disease, e.g. in form of special care programs. Regarding microbiological findings, no major differences between KT and HD patients were found.
Topics: Adult; Aged; Cross-Sectional Studies; Dental Plaque; Dental Plaque Index; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mouth; Oral Health; Periodontal Attachment Loss; Periodontal Index; Renal Dialysis
PubMed: 27531498
DOI: 10.1186/s12903-016-0274-0 -
Developmental Dynamics : An Official... Jul 2021Organs that develop early in life, and are replaced by a larger version as the animal grows, often represent a miniature version of the adult organ. Teeth constituting...
BACKGROUND
Organs that develop early in life, and are replaced by a larger version as the animal grows, often represent a miniature version of the adult organ. Teeth constituting the first functional dentition in small-sized teleost fish, such as medaka (Oryzias latipes), are examples of such miniature organs. With a dentin cone as small as the size of one human cell, or even smaller, these teeth raise the question how many dentin-producing cells (odontoblasts) are required to build such a tooth, and whether this number can be as little as one.
RESULTS
Based on detailed observations with transmission electron microscopy (TEM) and TEM-based 3D-reconstructions, we show that only one mesenchymal cell qualifies as a true odontoblast. A second mesenchymal cell potentially participates in dentin formation, but only at a late stage of tooth development. Moreover, the fate of these cells appears to be specified very early during tooth development.
CONCLUSIONS
Our observations indicate that in this system, one single odontoblast fulfills roles normally exerted by a large and communicating cell population. First-generation teeth in medaka thus provide an exciting model to study integration of multiple functions into a single cell.
Topics: Animals; Cell Count; Cell Differentiation; Cell Lineage; Computer Simulation; Embryo, Nonmammalian; Imaging, Three-Dimensional; Mesenchymal Stem Cells; Miniaturization; Morphogenesis; Odontoblasts; Odontogenesis; Oryzias; Tooth; Tooth Eruption
PubMed: 33452709
DOI: 10.1002/dvdy.300