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Biogerontology Aug 2023Dental pulp under physiological conditions has a defense function, repair capacity, and important mechanisms in pathological processes. In addition, the dental papilla... (Review)
Review
Dental pulp under physiological conditions has a defense function, repair capacity, and important mechanisms in pathological processes. In addition, the dental papilla is involved in important defense processes and an essential function in the pulp revascularization process. It is known that dental pulp and apical papilla undergo a natural aging process, in addition to stressful situations such as bruxism, inflammation, and infections. Both aging and stressful situations can lead to cellular senescence. Some evidence indicates that the changes resulting from this cellular state can directly affect the efficiency of cells in these tissues and affect conservative and regenerative clinical treatments. Thus, it is necessary to understand the causes and consequences of cellular senescence in addition to the development of methods for senescence prevention. This review aims to provide an overview of possible causes and consequences of senescence in dental pulp and stem cells from apical papilla and discusses possible methods to prevent this cellular state.
Topics: Humans; Dental Pulp; Cellular Senescence; Stem Cells; Aging; Inflammation; Cell Differentiation
PubMed: 37010664
DOI: 10.1007/s10522-023-10029-y -
Forensic Science International. Genetics Nov 2023Teeth are one of the body tissues remaining after severe decomposition from which a DNA profile can be obtained to aid in human identification. Currently, the standard...
Teeth are one of the body tissues remaining after severe decomposition from which a DNA profile can be obtained to aid in human identification. Currently, the standard approach to isolate DNA from teeth requires pulverizing the entire tooth. This destructive approach compromises any further morphological or anthropological study. We report on two methods of DNA isolation that minimizes destruction of the tooth when accessing the DNA within pulp and cementum. Forty-nine teeth, removed as part of normal dental procedures, were buried for up to 92 days, with a further nine teeth acting as unburied controls. Additionally, four teeth samples collected during a forensic examination were included in this study. The two processes were: using a fine drill to access the pulp from the crown and then using endodontic files to collect the biological material; and using a sterile blade to scrape the cementum. It was found that the samples collected from the cementum had greater DNA quality compared to those samples obtained from the pulp. Microbial activity was found to play a role in the degradation of the nuclear material, reducing DNA yields from pulp. DNA profiling data from 24 loci, including 22 STR markers, indicated that multi-rooted teeth provided better DNA quantity and quality than those with a single root. The DNA quantity obtained from pulp samples of teeth which exhibited cavities was adversely affected, although this DNA loss was not from samples collected from the cementum of teeth in similar condition. Obtaining samples from DNA profiling from the cementum was found to be ideal if the morphological preservation of the tooth is required. Obtaining pathogen DNA is of interest when an occlusal approach to retrieve pulp may serve as a good alternative to prepare DNA without destruction of the tooth structure.
Topics: Humans; Dental Cementum; Dental Pulp; Tooth; DNA; Tooth Crown
PubMed: 37844374
DOI: 10.1016/j.fsigen.2023.102945 -
Cells Feb 2024The dental pulp is the inner part of the tooth responsible for properly functioning during its lifespan. Apart from the very big biological heterogeneity of dental... (Review)
Review
The dental pulp is the inner part of the tooth responsible for properly functioning during its lifespan. Apart from the very big biological heterogeneity of dental cells, tooth microenvironments differ a lot in the context of mechanical properties-ranging from 5.5 kPa for dental pulp to around 100 GPa for dentin and enamel. This physical heterogeneity and complexity plays a key role in tooth physiology and in turn, is a great target for a variety of therapeutic approaches. First of all, physical mechanisms are crucial for the pain propagation process from the tooth surface to the nerves inside the dental pulp. On the other hand, the modulation of the physical environment affects the functioning of dental pulp cells and thus is important for regenerative medicine. In the present review, we describe the physiological significance of biomechanical processes in the physiology and pathology of dental pulp. Moreover, we couple those phenomena with recent advances in the fields of bioengineering and pharmacology aiming to control the functioning of dental pulp cells, reduce pain, and enhance the differentiation of dental cells into desired lineages. The reviewed literature shows great progress in the topic of bioengineering of dental pulp-although mainly in vitro. Apart from a few positions, it leaves a gap for necessary filling with studies providing the mechanisms of the mechanical control of dental pulp functioning in vivo.
Topics: Dental Pulp; Tooth; Regenerative Medicine; Cell Differentiation; Biophysics
PubMed: 38474339
DOI: 10.3390/cells13050375 -
Journal of Endodontics Aug 2023Understanding the healing process of dental pulp after tooth autotransplantation (TAT) and regenerative endodontic treatment (RET) of immature teeth is important both...
INTRODUCTION
Understanding the healing process of dental pulp after tooth autotransplantation (TAT) and regenerative endodontic treatment (RET) of immature teeth is important both clinically and scientifically. This study aimed to characterize the pattern of dental pulp healing in human teeth that underwent TAT and RET using state-of-the-art imaging techniques.
MATERIALS AND METHODS
This study examined 4 human teeth, 2 premolars that underwent TAT, and 2 central incisors that received RET. The premolars were extracted after 1 year (case 1) and 2 years (case 2) due to ankylosis, while the central incisors were extracted after 3 years (cases 3 and 4) for orthodontic reasons. Nanofocus x-ray computed tomography was used to image the samples before being processed for histological and immunohistochemical analysis. Laser scanning confocal second harmonic generation imaging (SHG) was used to examine the patterns of collagen deposition. A maturity-matched premolar was included as a negative control for the histological and SHG analysis.
RESULTS
Analysis of the 4 cases revealed different patterns of dental pulp healing. Similarities were observed in the progressive obliteration of the root canal space. However, a striking loss of typical pulpal architecture was observed in the TAT cases, while a pulp-like tissue was observed in one of the RET cases. Odontoblast-like cells were observed in cases 1 and 3.
CONCLUSIONS
This study provided insights into the patterns of dental pulp healing after TAT and RET. The SHG imaging sheds light on the patterns of collagen deposition during reparative dentin formation.
Topics: Humans; Dental Pulp; Regeneration; Regenerative Endodontics; Transplantation, Autologous; Dental Pulp Necrosis; Collagen; Multimodal Imaging
PubMed: 37315781
DOI: 10.1016/j.joen.2023.06.003 -
The Saudi Dental Journal Jul 2023Although there have been many studies on stem cells, few have investigated how neurotransmitters and stem cell proliferation interact to regenerate dental pulp. Dental... (Review)
Review
INTRODUCTION
Although there have been many studies on stem cells, few have investigated how neurotransmitters and stem cell proliferation interact to regenerate dental pulp. Dental pulp regeneration is an innovative procedure for reviving dental pulp, if feasible for the entire tooth. Upon tooth injury, activated platelets release serotonin and dopamine in bulk to mobilize dental pulp stem cells to mediate natural dental repair. This has induced research on the role of neurotransmitters in increasing the proliferation rate of stem cells. This review also covers prospective future treatments for dental pulp regeneration.
METHODS
A literature search was performed via PubMed and ScienceDirect from 2001 to 2022, using the keywords "neurotransmitter," "stem cell," "tooth regeneration," "tooth repair," "regenerative dentistry," and "dental pulp." Different inclusion/exclusion criteria were used, and the search was restricted to English articles.
RESULTS
Nine publications reporting neurotransmitter interactions with stem cells for tooth and pulp regeneration were selected.
CONCLUSION
Neurotransmitters were found to interact with dental stem cells. Evidence pointing to neurotransmitters as a factor in the increased proliferation of stem cells was found. This review thus gives hope for tooth pulp regeneration and repair.
PubMed: 37520592
DOI: 10.1016/j.sdentj.2023.05.004 -
International Endodontic Journal Oct 2023The diagnosis of the status of the inflamed pulp is essential in clinical diagnosis and treatment provision. There are a limited number of well-designed and... (Review)
Review
BACKGROUND
The diagnosis of the status of the inflamed pulp is essential in clinical diagnosis and treatment provision. There are a limited number of well-designed and well-executed clinical trials on the diagnosis of the true status of the pulp.
OBJECTIVES
Three PICO questions were formulated and agreed a priori by the European Society of Endodontology to evaluate the clinical tests for sensibility testing, determination of biomarkers and pulp bleeding with regard to their suitability to correctly diagnose the condition of the pulp tissue for the development of S3-Level guidelines.
METHODS
A literature search was conducted using PubMed, Clarivate Analytics' Web of Science, Scopus, Google Scholar and Cochrane Central Register of Controlled Trials from inception to 21 January 2022. Additionally, a hand search was performed, and the contents of the major subject journals were also examined. Eligibility criteria followed the proposed PICO questions. Two independent reviewers were involved in study selection, data extraction and appraising the included studies; disagreements were resolved by a third reviewer. The risk of bias was assessed by the QUADAS-2 tool for diagnostic accuracy studies, the Newcastle-Ottawa scale for noncomparative, nonrandomized studies and the Newcastle-Ottawa Quality Assessment scale adapted for cross-sectional studies.
RESULTS
In total, 28 studies out of 29 publications were considered eligible and were included in the review. Twelve studies were identified to investigate the diagnostic accuracy of the pulp vitality. Ten studies fulfilled the criteria to evaluate the diagnostic accuracy of the pulpal conditions, while 6 studies investigating the expression of biomarkers were eligible. Three studies addressing the prognostic factors and therapeutic interventions relating to pulpal status were included.
DISCUSSION
The core problem in pulp diagnostics is that a reliable reference standard is lacking under clinical conditions. Based on limited evidence, the most promising current approach seems to define a combination of different clinical tests and symptoms, probably in future including molecular diagnosis ("diagnostic package") will be required to ascertain the best possible strategy to clinically diagnose true pulpal conditions.
CONCLUSIONS
The effectiveness of diagnosing pulpitis is low due to limited scientific evidence regarding the accuracy and reproducibility of diagnostic tests. There is a lack of evidence to determine the true status of the pulp or to identify prognostic indicators allowing for a reliable pre-operative estimation of the outcome of vital pulp treatment.
REGISTRATION
PROSPERO database (CRD42021265366).
Topics: Humans; Pulpitis; Cross-Sectional Studies; Reproducibility of Results; Dental Pulp; Dental Pulp Diseases; Biomarkers
PubMed: 35536159
DOI: 10.1111/iej.13762 -
International Endodontic Journal Aug 2023Biallelic loss-of-function FAM20A mutations cause amelogenesis imperfecta (AI) type IG, better known as enamel renal syndrome (ERS), characterized by severe enamel...
AIM
Biallelic loss-of-function FAM20A mutations cause amelogenesis imperfecta (AI) type IG, better known as enamel renal syndrome (ERS), characterized by severe enamel hypoplasia, delayed/failed tooth eruption, intrapulpal calcifications, gingival hyperplasia and nephrocalcinosis. FAM20A binds to FAM20C, the Golgi casein kinase (GCK) and potentiates its function to phosphorylate secreted proteins critical for biomineralization. While many FAM20A pathogenic mutations have been reported, the pathogeneses of orodental anomalies in ERS remain to be elucidated. This study aimed to identify disease-causing mutations for patients with ERS phenotypes and to discern the molecular mechanism underlying ERS intrapulpal calcifications.
METHODOLOGY
Phenotypic characterization and whole exome analyses were conducted for 8 families and 2 sporadic cases with hypoplastic AI. A minigene assay was performed to investigate the molecular consequences of a FAM20A splice-site variant. RNA sequencing followed by transcription profiling and gene ontology (GO) analyses were carried out for dental pulp tissues of ERS and the control.
RESULTS
Biallelic FAM20A mutations were demonstrated for each affected individual, including 7 novel pathogenic variants: c.590-5T>A, c.625T>A (p.Cys209Ser), c.771del (p.Gln258Argfs*28), c.832_835delinsTGTCCGACGGTGTCCGACGGTGTC CA (p.Val278Cysfs*29), c.1232G>A (p.Arg411Gln), c.1297A>G (p.Arg433Gly) and c.1351del (p.Gln451Serfs*4). The c.590-5T>A splice-site mutation caused Exon 3 skipping, which resulted in an in-frame deletion of a unique region of the FAM20A protein, p.(Asp197_Ile214delinsVal). Analyses of differentially expressed genes in ERS pulp tissues demonstrated that genes involved in biomineralization, particularly dentinogenesis, were significantly upregulated, such as DSPP, MMP9, MMP20 and WNT10A. Enrichment analyses indicated overrepresentation of gene sets associated with BMP and SMAD signalling pathways. In contrast, GO terms related to inflammation and axon development were underrepresented. Among BMP signalling genes, BMP agonists GDF7, GDF15, BMP3, BMP8A, BMP8B, BMP4 and BMP6 were upregulated, while BMP antagonists GREM1, BMPER and VWC2 showed decreased expression in ERS dental pulp tissues.
CONCLUSIONS
Upregulation of BMP signalling underlies intrapulpal calcifications in ERS. FAM20A plays an essential role in pulp tissue homeostasis and prevention of ectopic mineralization in soft tissues. This critical function probably depends upon MGP (matrix Gla protein), a potent mineralization inhibitor that must be properly phosphorylated by FAM20A-FAM20C kinase complex.
Topics: Humans; Nephrocalcinosis; Amelogenesis Imperfecta; Dental Pulp; Dental Enamel Proteins; Mutation; Calcinosis; Gene Expression Profiling; Carrier Proteins
PubMed: 37159186
DOI: 10.1111/iej.13928 -
Frontiers in Bioscience (Landmark... Oct 2023Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells derived from dental pulp that serves as an important model for investigating biological regeneration.... (Review)
Review
Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells derived from dental pulp that serves as an important model for investigating biological regeneration. DPSCs have a multipotent differentiation capacity and can promote different biological processes, including osteogenesis, odontogenesis, chondrogenesis, and angiogenesis. These biological processes are regulated by an extensive range of intra- and extra-cellular factors. Further, biomechanical cues, such as substrate stiffness, physical stress, and cell spreading, have been highlighted as particularly important modulators of DPSC function. This review sought to discuss various related signaling components involved in biomechanical cues and their respective roles in cellular and tissue responses in DPSCs, summarize current findings, and provide an outlook on the potential applications of biomechanics in regenerative medicine and tissue engineering.
Topics: Stem Cells; Dental Pulp; Cell Differentiation; Osteogenesis; Mesenchymal Stem Cells; Cells, Cultured; Cell Proliferation
PubMed: 37919075
DOI: 10.31083/j.fbl2810274 -
MicroRNA and their implications in dental pulp inflammation: current trends and future perspectives.Odontology Jul 2023MicroRNAs (miRNAs) are short, 19-23 nucleotide non-coding RNA molecules that regulate gene expression by silencing or degrading the target mRNA gene. Since their... (Review)
Review
MicroRNAs (miRNAs) are short, 19-23 nucleotide non-coding RNA molecules that regulate gene expression by silencing or degrading the target mRNA gene. Since their discovery in the nineties of the last century, they have emerged as key inflammatory regulators. Inflammation induces the synthesis of various miRNAs that modulate the expression of multiple molecules involved in orchestrating the inflammatory response. This review aims to provide an insight into the role of miRNAs as potential biomarkers, mediators, and potential therapeutic targets of dental pulp inflammation. A literature search was conducted using the keywords; biogenesis of microRNA, human dental pulp cells, pulpitis, and inflammation in PubMed and Scopus index databases for all the published articles dealing with the role of miRNAs in pulp inflammation in the last 10 years. According to the literature, there is a clear correlation between miRNAs and several physiological events, as well as their role as mediators of innate immune response and inflammation in dental pulp cells. Our narrative review stipulates that numerous miRNAs play a key role in modulating inflammation, delaying or enhancing cell repair, cell differentiation, and survival in dental pulp diseases. However, further studies are required for the validation of miRNAs as reliable biomarkers in dental pulp pathology and their targeted therapy.
Topics: Humans; MicroRNAs; Dental Pulp; Inflammation; Pulpitis; Biomarkers
PubMed: 36309897
DOI: 10.1007/s10266-022-00762-0 -
Biomaterials and Biosystems Sep 2023Mesenchymal stromal/stem cell (MSC) therapies are currently being explored for dental pulp regeneration. As the therapeutic effects of MSCs in tissue repair are mediated...
Mesenchymal stromal/stem cell (MSC) therapies are currently being explored for dental pulp regeneration. As the therapeutic effects of MSCs in tissue repair are mediated mainly through the release of extracellular vesicles (EVs) including exosomes, we investigated here the cellular processes and molecular mechanisms modulated by MSC exosomes in dental pulp regeneration. Using dental pulp cell (DPC) cultures, we demonstrated that MSC exosomes could increase DPC migration, proliferation, and odontogenic differentiation. The enhancement of these cellular processes was mediated through exosomal CD73-mediated adenosine receptor activation of AKT and ERK signaling. Consistent with these observations, MSC exosomes increased the expression of dentin matrix proteins and promoted the formation of dentin-like tissue and bridge-like structures in a rat pulp defect model. These effects were comparable to that of mineral trioxide aggregate (MTA) treatment. MSC exosomes also yielded recellularized pulp-dentin tissues in the root canal of endodontically-treated human premolars, following subcutaneous implantation in the mouse dorsum. Together, our findings suggest that MSC exosomes could exert a multi-faceted effect on DPC functions including migration, proliferation and odontogenic differentiation to promote dental pulp regeneration. This study provides the basis for development of MSC exosomes as a cell-free MSC therapeutic alternative for pulp-dentin regeneration.
PubMed: 37283805
DOI: 10.1016/j.bbiosy.2023.100078