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Current Stem Cell Research & Therapy 2021Oral diseases, such as dental caries, pulpitis, periodontitis, and craniofacial trauma, are common. Some individuals suffer from oral cancer or congenital craniofacial... (Review)
Review
Oral diseases, such as dental caries, pulpitis, periodontitis, and craniofacial trauma, are common. Some individuals suffer from oral cancer or congenital craniofacial defects. The oral-systemic disease link reveals that a dental disorder is not a minor problem. Tissue loss is an inevitable consequence of most oral diseases, and repairing the tissue loss and restoring craniofacial function are highly expected by patients and are terminal targets of dental treatment. The current clinical approach for tissue loss due to dental caries, pulpitis, periodontitis, oral cancer, trauma, and developmental diseases depends on the filling of corresponding material, allograft, or autograft bone after lesion removal. Repair of the tissue volume is expectedly followed by promising functional restoration using regenerative dental tissue or tissue engineering, which has currently aroused the interest of clinicians and researchers. This review focuses on the ideas and recent findings on newly identified skeletal stem cells (SSCs) as candidates for craniofacial regeneration, signaling regulation of SSCs extended from embryonic development, and signal molecule delivery for the repair of the craniofacial defect, sincerely hoping that the hypothesis of craniofacial self-healing is true in the future.
Topics: Dental Caries; Humans; Periodontitis; Pulpitis; Regeneration; Regenerative Medicine; Stem Cells; Tissue Engineering; Wounds and Injuries
PubMed: 33511958
DOI: 10.2174/1574888X16999210128193910 -
Clinical Oral Investigations Mar 2022The concept of minimally invasive endodontics recommends less-invasive vital pulp therapy (VPT) modalities over more aggressive traditional endodontic approaches in... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The concept of minimally invasive endodontics recommends less-invasive vital pulp therapy (VPT) modalities over more aggressive traditional endodontic approaches in mature permanent teeth with carious pulp exposure, including irreversible pulpitis (IP) cases. Consequently, VPT needs to be compared with root canal therapy (RCT) in terms of treatment outcomes. This randomized clinical trial compares the results of full pulpotomy using two calcium-silicate cements, i.e., mineral trioxide aggregate (MTA) and calcium-enriched mixture (CEM) cement, with RCT in mature permanent teeth.
MATERIALS AND METHODS
A total of 157 carious pulp exposure cases in two academic centers with/without established IP were selected/included/randomly appointed to three study arms; (i) RCT (n = 51) as the reference treatment, (ii) pulpotomy with ProRoot MTA (PMTA; n = 55), and (iii) pulpotomy with CEM cement (PCEM; n = 51) as two alternative VPT treatments. Two-year clinical/radiographic results were the outcomes of interest. Data were statistically analyzed through the analysis of variance, chi-square, Fisher exact test, and Kruskal-Wallis.
RESULTS
At 2-year recall, 147 teeth were examined (6.4% dropout). All molars, except for one, were clinically functional/symptom-free, and there was no statistical difference between the three study arms (p = 0.653). The radiographic success rates in RCT, PMTA, and PCEM arms were 98%, 100%, and 97.9%, respectively, without statistically significant differences (p = 0.544).
CONCLUSION
In the management of mature permanent teeth with/without established IP, all experimental groups exhibited equivalent/comparable results.
CLINICAL RELEVANCE
Simple VPT using MTA/CEM can be suggested/recommended as a viable advantageous alternative to RCT for the management of carious pulp exposures with/without sign/symptoms of IP.
Topics: Aluminum Compounds; Biocompatible Materials; Calcium Compounds; Drug Combinations; Humans; Molar; Oxides; Pulpitis; Pulpotomy; Root Canal Therapy; Silicates
PubMed: 34854987
DOI: 10.1007/s00784-021-04310-y -
International Immunopharmacology Jul 2023DNA damage-inducible transcript 3 (DDIT3), a stress response gene, engages in the physiological and pathological processes of organisms, whereas its impact on pulpitis...
DNA damage-inducible transcript 3 (DDIT3), a stress response gene, engages in the physiological and pathological processes of organisms, whereas its impact on pulpitis has not been defined yet. It has been demonstrated that macrophage polarization has a significant impact on inflammation. This research intends to investigate the effect of DDIT3 on the inflammation of pulpitis and macrophage polarization. C57BL/6J mice were used to model experimental pulpitis at 6, 12, 24, and 72 h after pulp exposure, with untreated mice as the control. The progression of pulpitis was visible histologically, and DDIT3 showed a trend of initially upward and downward later. Compared with wild-type mice, inflammatory cytokines and M1 macrophages were reduced, while M2 macrophages were increased in DDIT3 knockout mice. In RAW264.7 cells and bone borrow-derived macrophages, DDIT3 was found to enhance M1 polarization while impair M2 polarization. Targeted knockdown of early growth response 1 (EGR1) could rescue the blocking effect of DDIT3 deletion on M1 polarization. In conclusion, our results indicated that DDIT3 could exacerbate inflammation of pulpitis through the regulation of macrophage polarization, and DDIT3 could promote M1 polarization by inhibiting EGR1. It provides a new target for pulpitis treatment and tissue regeneration in the future.
Topics: Animals; Mice; Inflammation; Macrophages; Mice, Inbred C57BL; Pulpitis; RAW 264.7 Cells
PubMed: 37235961
DOI: 10.1016/j.intimp.2023.110328 -
International Endodontic Journal Mar 2023The aim of this study was to assess and compare the clinical and radiographic outcome of partial pulpotomy and full pulpotomy using Biodentine in cariously exposed... (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
The aim of this study was to assess and compare the clinical and radiographic outcome of partial pulpotomy and full pulpotomy using Biodentine in cariously exposed mature molar teeth with symptoms indicative of irreversible pulpitis.
METHODOLOGY
This study is an unicentric, double-arm, randomized superiority clinical trial with parallel experimental groups, registered under CTRI (CTRI/2019/12/022559). Fifty mature permanent molar teeth with carious exposures with symptoms indicative of irreversible pulpitis were randomly allocated equally into two groups. Partial pulpotomy (PP) and full pulpotomy (FP) were performed in the first and second group, respectively, following standardized protocols. Exposed pulp tissue was removed up to a depth of 2-3 mm for partial pulpotomy, whereas complete coronal pulp tissue was removed up to the level of root orifices for full pulpotomy. Haemostasis was achieved with placement of 2.5% sodium hypochlorite-moistened cotton pellets placed on amputated pulp tissue for a maximum of 10 min. Biodentine was used as the pulp capping material. Pain scores were evaluated using 11-point Visual Analogue Scale (VAS) preoperatively, at 24 h, 48 h and 7th day after the intervention(s). Clinical and radiographic evaluation was done at 3 months, 6 months and 1 year. The data were statistically analysed using chi-squared test, Mann-Whitney U-test, Friedman's test and Wilcoxon signed-rank test. The significance level was pre-determined at p < .05. Cumulative survival probabilities were assessed at 12 months using Kaplan-Meier analysis.
RESULTS
Intra-group analysis of pain scores revealed significant reduction in pain scores preoperatively and at 24 h, 48 h and 7th day in both the groups. However, the difference in the pain score(s) reduction between both the groups was not statistically significant at any time interval (p > .05). At 1-year follow-up, the success rate was 88% (22/25) and 91.6% (22/24) for PP and FP respectively (p > .05).
CONCLUSIONS
Partial pulpotomy showed comparable results to full pulpotomy in terms of clinical/radiographic treatment outcome. If the long-term results remain the same, partial pulpotomy can be proposed as an alternative treatment modality for mature teeth with cariously exposed pulp tissue presenting with signs of symptomatic irreversible pulpitis.
Topics: Humans; Pulpotomy; Pulpitis; Calcium Compounds; Molar; Silicates; Treatment Outcome; Pain; Oxides; Drug Combinations; Aluminum Compounds
PubMed: 36403208
DOI: 10.1111/iej.13872 -
Journal of Endodontics Oct 2020Regulated cell death (RCD) is a preferred term inclusive of all modes of cell death regulated by multiple intracellular signal transduction pathways under physiological... (Review)
Review
Regulated cell death (RCD) is a preferred term inclusive of all modes of cell death regulated by multiple intracellular signal transduction pathways under physiological and pathologic conditions. Although cell death programs ensure correct growth and developmental processes as well as protect the host against microbial pathogens, some necrotic cell death pathways, such as pyroptosis, NETosis, and necroptosis, release intracellular damage-associated molecular patterns and inflammatory cytokines, thereby skewing the milieu toward a proinflammatory state. Pulpitis is 1 of the most prevalent oral inflammatory diseases. In response to different types of pulpal injury, RCD may occur either in a "single" or an "overlapped mixed" form, including apoptosis, pyroptosis, and NETosis, which can indicate the severity of pulpal inflammation. RCD has received increasing attention because of the cross talk among cell death pathways. Hence, understanding the molecular switch nodes mediating cross talk between diverse RCD pathways may provide new insights into mechanisms underlying cell-fate decision in pulpitis. In this review, we outlined the potential roles of RCD in the progression of pulpitis and some switch nodes connecting different RCD pathways. Ultimately, an in-depth understanding of molecular mechanisms underlying RCD could be translated into effective approaches to preserve pulpal vitality and integrity under pathologic conditions.
Topics: Apoptosis; Humans; Necrosis; Pulpitis; Pyroptosis; Regulated Cell Death
PubMed: 32682790
DOI: 10.1016/j.joen.2020.07.006 -
International Journal of Molecular... Oct 2023Oral inflammatory diseases (OIDs) include many common diseases such as periodontitis and pulpitis. The causes of OIDs consist microorganism, trauma, occlusal factors,... (Review)
Review
Oral inflammatory diseases (OIDs) include many common diseases such as periodontitis and pulpitis. The causes of OIDs consist microorganism, trauma, occlusal factors, autoimmune dis-eases and radiation therapy. When treated unproperly, such diseases not only affect oral health but also pose threat to people's overall health condition. Therefore, identifying OIDs at an early stage and exploring new therapeutic strategies are important tasks for oral-related research. Mitochondria are crucial organelles for many cellular activities and disruptions of mitochondrial function not only affect cellular metabolism but also indirectly influence people's health and life span. Mitochondrial dysfunction has been implicated in many common polygenic diseases, including cardiovascular and neurodegenerative diseases. Recently, increasing evidence suggests that mitochondrial dysfunction plays a critical role in the development and progression of OIDs and its associated systemic diseases. In this review, we elucidated the critical insights into mitochondrial dysfunction and its involvement in the inflammatory responses in OIDs. We also summarized recent research progresses on the treatment of OIDs targeting mitochondrial dysfunction and discussed the underlying mechanisms.
Topics: Humans; Oxidative Stress; Mitochondria; Periodontitis; Longevity; Pulpitis; Mitochondrial Diseases
PubMed: 37895162
DOI: 10.3390/ijms242015483 -
Cell Proliferation Sep 2023Mitochondrial transfer is emerging as a promising therapeutic strategy for tissue repair, but whether it protects against pulpitis remains unclear. Here, we show that...
Mitochondrial transfer is emerging as a promising therapeutic strategy for tissue repair, but whether it protects against pulpitis remains unclear. Here, we show that hyperactivated nucleotide-binding domain and leucine-rich repeat protein3 (NLRP3) inflammasomes with pyroptotic cell death was present in pulpitis tissues, especially in the odontoblast layer, and mitochondrial oxidative stress (OS) was involved in driving this NLRP3 inflammasome-induced pathology. Using bone marrow mesenchymal stem cells (BMSCs) as mitochondrial donor cells, we demonstrated that BMSCs could donate their mitochondria to odontoblasts via tunnelling nanotubes (TNTs) and, thus, reduce mitochondrial OS and the consequent NLRP3 inflammasome-induced pyroptosis in odontoblasts. These protective effects of BMSCs were mostly blocked by inhibitors of the mitochondrial function or TNT formation. In terms of the mechanism of action, TNF-α secreted from pyroptotic odontoblasts activates NF-κB signalling in BMSCs via the paracrine pathway, thereby promoting the TNT formation in BMSCs and enhancing mitochondrial transfer efficiency. Inhibitions of NF-κB signalling and TNF-α secretion in BMSCs suppressed their mitochondrial donation capacity and TNT formation. Collectively, these findings demonstrated that TNT-mediated mitochondrial transfer is a potential protective mechanism of BMSCs under stress conditions, suggesting a new therapeutic strategy of mitochondrial transfer for dental pulp repair.
Topics: Humans; Pyroptosis; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; NF-kappa B; Tumor Necrosis Factor-alpha; Pulpitis; Dental Pulp; Mitochondria
PubMed: 37086012
DOI: 10.1111/cpr.13442 -
Cell Biology International Jan 2022Wnts include more than 19 types of secreted glycoproteins that are involved in a wide range of pathological processes in oral and maxillofacial diseases. The... (Review)
Review
Wnts include more than 19 types of secreted glycoproteins that are involved in a wide range of pathological processes in oral and maxillofacial diseases. The transmission of Wnt signalling from the extracellular matrix into the nucleus includes canonical pathways and noncanonical pathways, which play an important role in tooth development, alveolar bone regeneration, and related diseases. In recent years, with the in-depth study of Wnt signalling in oral and maxillofacial-related diseases, many new conclusions and perspectives have been reached, and there are also some controversies. This article aims to summarise the roles of Wnt signalling in various oral diseases, including periodontitis, dental pulp disease, jaw disease, cleft palate, and abnormal tooth development, to provide researchers with a better and more comprehensive understanding of Wnts in oral and maxillofacial diseases.
Topics: Animals; Dental Caries; Gene Expression Regulation; Humans; Mouth; Odontogenesis; Periapical Periodontitis; Periodontal Diseases; Pulpitis; Temporomandibular Joint Dysfunction Syndrome; Tooth Diseases; Wnt Proteins; Wnt Signaling Pathway
PubMed: 34643311
DOI: 10.1002/cbin.11708 -
Journal of Dental Research Dec 2023Vital pulp therapy and root canal therapy (RCT) are the dominant treatment for irreversible pulpitis. While the success rate of these procedures is favorable, they have...
Vital pulp therapy and root canal therapy (RCT) are the dominant treatment for irreversible pulpitis. While the success rate of these procedures is favorable, they have some limitations. For instance, RCT leads to removing significant dentin in the coronal third of the tooth that increases root-fracture risk, which forces tooth removal. The ideal therapeutic goal is dental pulp regeneration, which is not achievable with RCT. Specialized proresolving mediators (SPMs) are well known for inflammatory resolution. The resolution of inflammation and tissue restoration or regeneration is a dynamic and continuous process. SPMs not only have potent immune-modulating functions but also effectively promote tissue homeostasis and regeneration. Resolvins have been shown to promote dental pulp regeneration. The purpose of this study was to explore further the cellular target of Resolvin E1 (RvE1) therapy in dental pulp regeneration and the impact of RvE1 in infected pulps. We investigated the actions of RvE1 on experimentally exposed pulps with or without microbial infection in an ; genetically defined mouse model. Our results showed RvE1 promoted Axin2-tdTomato cell expansion and odontoblastic differentiation after direct pulp capping in the mouse, which we used to mimic reversible pulpitis cases in the clinic. In cultured mouse dental pulp stem cells (mDPSCs), RvE1 facilitated Axin2-tdTomato cell proliferation and odontoblastic differentiation and also rescued impaired functions after lipopolysaccharide stimulation. In infected pulps exposed to the oral environment for 24 h, RvE1 suppressed inflammatory infiltration, reduced bacterial invasion in root canals, and prevented the development of apical periodontitis, while its proregenerative impact was limited. Collectively, topical treatment with RvE1 facilitated dental pulp regenerative properties by promoting Axin2-expressing cell proliferation and differentiation. It also modulated the resolution of inflammation, reduced infection severity, and prevented apical periodontitis, presenting RvE1 as a novel therapeutic for treating endodontic diseases.
Topics: Mice; Animals; Pulpitis; Dental Pulp; Periapical Periodontitis; Inflammation; Bacteria; Regeneration; Axin Protein
PubMed: 37837227
DOI: 10.1177/00220345231197156 -
BMC Oral Health Nov 2023N6-methyladenosine (mA) RNA modification regulators play an important role in many human diseases, and its abnormal expression can lead to the occurrence and development...
BACKGROUND
N6-methyladenosine (mA) RNA modification regulators play an important role in many human diseases, and its abnormal expression can lead to the occurrence and development of diseases. However, their significance in pulpitis remains largely unknown. Here, we sought to identify and validate the mA RNA regulatory network in pulpitis.
METHODS
Gene expression data for mA regulators in human pulpitis and normal pulp tissues from public GEO databases were analyzed. Bioinformatics analysis including Gene ontology (GO) functional, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed by R package, and Cytoscape software was used to study the role of mA miRNA-mRNA regulatory network in pulpitis. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression of key mA regulators in collected human pulpitis specimens.
RESULTS
Differential genes between pulpitis and normal groups were found from the GEO database, and further analysis found that there were significant differences in the mA modification-related genes ALKBH5, METTL14, METTL3, METTL16, RBM15B and YTHDF1. And their interaction relationships and hub genes were determined. The hub m6A regulator targets were enriched in immune cells differentiation, glutamatergic synapse, ephrin receptor binding and osteoclast differentiation in pulpitis. Validation by qRT-PCR showed that the expression of methylases METTL14 and METTL3 was decreased, thus these two genes may play a key role in pulpitis.
CONCLUSION
Our study identified and validated the mA RNA regulatory network in pulpitis. These findings will provide valuable resource to guide the mechanistic and therapeutic analysis of the role of key mA modulators in pulpitis.
Topics: Humans; Pulpitis; MicroRNAs; RNA, Messenger; Dental Pulp; Computational Biology; Methyltransferases
PubMed: 37978362
DOI: 10.1186/s12903-023-03578-8