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Biomedicines Dec 2023Dental pulp pericytes are reported to have the capacity to generate odontoblasts and express multiple cytokines and chemokines that regulate the local immune...
Dental pulp pericytes are reported to have the capacity to generate odontoblasts and express multiple cytokines and chemokines that regulate the local immune microenvironment, thus participating in the repair of dental pulp injury in vivo. However, it has not yet been reported whether the transplantation of exogenous pericytes can effectively treat pulpitis, and the underlying molecular mechanism remains unknown. In this study, using a lineage-tracing mouse model, we showed that most dental pulp pericytes are derived from cranial neural crest. Then, we demonstrated that the ablation of pericytes could induce a pulpitis-like phenotype in uninfected dental pulp in mice, and we showed that the significant loss of pericytes occurs during pupal inflammation, implying that the transplantation of pericytes may help to restore dental pulp homeostasis during pulpitis. Subsequently, we successfully generated pericytes with immunomodulatory activity from human pluripotent stem cells through the intermediate stage of the cranial neural crest with a high level of efficiency. Most strikingly, for the first time we showed that, compared with the untreated pulpitis group, the transplantation of hPSC-derived pericytes could substantially inhibit vascular permeability (the extravascular deposition of fibrinogen, ** < 0.01), alleviate pulpal inflammation (TCR cell infiltration, * < 0.05), and promote the regeneration of dentin (** < 0.01) in the mouse model of pulpitis. In addition, we discovered that the knockdown of latent transforming growth factor beta binding protein 1 () remarkably suppressed the immunoregulation ability of pericytes in vitro and compromised their in vivo regenerative potential in pulpitis. These results indicate that the transplantation of pericytes could efficiently rescue the aberrant phenotype of pulpal inflammation, which may be partially due to -mediated T cell suppression.
PubMed: 38137420
DOI: 10.3390/biomedicines11123199 -
European Endodontic Journal Aug 2023To investigate the concentration of Matrix metalloproteinases-9 (MMP-9) and Tumor necroses fac- tor-alpha (TNF- α) in pulpal blood at various stages of pulpal...
OBJECTIVE
To investigate the concentration of Matrix metalloproteinases-9 (MMP-9) and Tumor necroses fac- tor-alpha (TNF- α) in pulpal blood at various stages of pulpal inflammation in diabetics and to establish the relationship between these two biomarkers.
METHODS
77 patients, each having a tooth with pulpal exposure due to caries presenting with distinct stages of pulpitis were grouped into 2 main study groups as based on the HbA1c Levels-Group 1: Non-Diabetics (Control Group) (HbA1c < 5.6%) and Group 2: Type 2 Diabetics (Experimental Group) (HbA1c>6.5%; Random Plasma Glucose > 200) and diabetes mellitus with less than 10-year history. Depending on the radiological and clinical diagnosis, these two groups were again sub-divided into 2 subgroups: Sub-group A: Tooth with Symptomatic Irreversible Pulpitis. Sub Group B: Tooth with Reversible Pulpitis. Thus, for comparison purposes, a total of 4 sub-divisions were formed: Sub-group 1A- Non-Diabetic, Symtomatic Irreversible Pulpitis, Sub- group 1B: Non-Diabetic, Reversible Pulpitis, Sub-group 2A: Diabetic, Symptomatic Irreversible Pulpitis, Sub- group 2B: Diabetic, Reversible Pulpitis. Blood sample was collected from pulp chamber after partial pulpo- tomy was done. The total levels of MMP-9 and TNF-α were assessed by enzyme linked immunosorbent assays (ELISA). Inter-group comparison in levels of MMP-9 and TNF- α were conducted using the Kruskal Wallis test and pairwise comparison was done Mann-Whitney U test.
RESULTS
The inter-group comparison in levels of MMP-9 and TNF- α were conducted using the Kruskal Wallis test and pairwise comparison was done using Mann-Whitney U test. Pearson correlations were conducted in order to investigate correlations between the paired TNF-α and MMP-9 values and also their correlation with the blood sugar levels within the pulp diagnosis groups. MMP-9 and TNF-α levels were significantly higher (p<0.005) in irreversible pulpits than reversible pulpits and also in Type-2 diabetics than non-diabetics. High- est level of MMP-9 and TNF-α was found in Group 2A (Diabetic, symptomaticirreversible pulpitis) and lowest in Group 1B (Non-Diabetic, reversible pulpitis). There exists a very high significant positive correlation between MMP-9 and TNF-α (p<0.005).
CONCLUSION
These findings show that the inflammatory mediators MMP-9 and TNF-α are significantly in- creased in pulpal blood samples of diabetic patients. Also, in diabetic patients diagnosed with reversible pul- pitis, higher levels of inflammatory pulpal biomarkers were reported that could compromise the success of Vital Pulp Therapy (VPT) and may necessitate endodontic intervention. MMP-9 and TNF- α were reported to have a positive correlation. (EEJ-2023-01-04).
Topics: Humans; Biomarkers; Cross-Sectional Studies; Diabetes Mellitus; Glycated Hemoglobin; Inflammation; Matrix Metalloproteinase 9; Pulpitis; Tumor Necrosis Factor-alpha
PubMed: 38219033
DOI: 10.14744/eej.2023.41736 -
International Dental Journal Oct 2023The dysregulated long noncoding RNAs (lncRNAs) are implicated in progression of various diseases, including pulpitis. Double homeobox A pseudogene 8 (DUXAP8) has been...
BACKGROUND
The dysregulated long noncoding RNAs (lncRNAs) are implicated in progression of various diseases, including pulpitis. Double homeobox A pseudogene 8 (DUXAP8) has been found to be upregulated in pulpitis. Herein, the functional mechanism of DUXAP8 in lipopolysaccharide (LPS)-induced pulpitis was explored.
MATERIAL AND METHODS
DUXAP8, microRNA-18b-5p (miR-18b-5p), or hypoxia-inducible factor 3A (HIF3A) levels were examined through reverse transcription-quantitative polymerase chain reaction assay. Cell behaviours were determined by Cell Counting Kit-8 assay for cell viability, Ethynyl-2'-deoxyuridine (EdU) assay for cell proliferation, and flow cytometry for cell apoptosis. Protein levels were measured using western blot. Inflammatory reaction was analysed via enzyme-linked immunosorbent assay. Oxidative stress was assessed by commercial kits. Dual-luciferase reporter assay, RNA immunoprecipitation assay, and pull-down assay were used for validation of interaction between targets.
RESULTS
Cell apoptosis, inflammatory reaction, and oxidative stress were induced by LPS in human dental pulp cells (HDPCs). DUXAP8 upregulation and miR-18b-5p downregulation were found in pulpitis. LPS-induced cell injury was relieved after downregulation of DUXAP8. DUXAP8 interacted with miR-18b-5p. The regulation of DUXAP8 was related to miR-18b-5p sponging function in LPS-treated HDPCs. HIF3A served as a target of miR-18b-5p. MiR-18b-5p protected against LPS-induced cell injury through targeting HIF3A. DUXAP8 targeted miR-18b-5p to regulate HIF3A level.
CONCLUSIONS
Results demonstrated that LPS-induced cell injury in pulpitis was promoted by DUXAP8 through mediating miR-18b-5p/HIF3A axis.
Topics: Humans; Genes, Homeobox; Lipopolysaccharides; Pulpitis; Pseudogenes; MicroRNAs; Repressor Proteins; Apoptosis Regulatory Proteins
PubMed: 36522211
DOI: 10.1016/j.identj.2022.11.011 -
Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi... Dec 2023Traditionally, vital pulp therapy (VPT) is mainly indicated for young permanent teeth. However, in recent years, VPT has been increasingly applied to mature permanent...
Traditionally, vital pulp therapy (VPT) is mainly indicated for young permanent teeth. However, in recent years, VPT has been increasingly applied to mature permanent teeth. VPT was previously thought to be effective only for teeth with normal pulp or reversible pulpitis. However, an increasing body of evidence has demonstrated that VPT can successfully manage permanent teeth with irreversible pulpitis or apical periodontitis. This work discusses which teeth with irreversible pulpitis or apical periodontitis are suitable for VPT, the recommended method to evaluate and select this kind of case, and the clinical procedure involved to operate such a case.
Topics: Humans; Pulpitis; Dental Pulp; Dentition, Permanent; Periapical Periodontitis; Dental Care; Pulpotomy
PubMed: 38597025
DOI: 10.7518/hxkq.2023.2023193 -
The role of autophagy in odontogenesis, dental implant surgery, periapical and periodontal diseases.Journal of Cellular and Molecular... Apr 2024Autophagy is a cellular process that is evolutionarily conserved, involving the sequestration of damaged organelles and proteins into autophagic vesicles, which... (Review)
Review
Autophagy is a cellular process that is evolutionarily conserved, involving the sequestration of damaged organelles and proteins into autophagic vesicles, which subsequently fuse with lysosomes for degradation. Autophagy controls the development of many diseases by influencing apoptosis, inflammation, the immune response and different cellular processes. Autophagy plays a significant role in the aetiology of disorders associated with dentistry. Autophagy controls odontogenesis. Furthermore, it is implicated in the pathophysiology of pulpitis and periapical disorders. It enhances the survival, penetration and colonization of periodontal pathogenic bacteria into the host periodontal tissues and facilitates their escape from host defences. Autophagy plays a crucial role in mitigating exaggerated inflammatory reactions within the host's system during instances of infection and inflammation. Autophagy also plays a role in the relationship between periodontal disease and systemic diseases. Autophagy promotes wound healing and may enhance implant osseointegration. This study reviews autophagy's dento-alveolar effects, focusing on its role in odontogenesis, periapical diseases, periodontal diseases and dental implant surgery, providing valuable insights for dentists on tooth development and dental applications. A thorough examination of autophagy has the potential to discover novel and efficacious treatment targets within the field of dentistry.
Topics: Humans; Dental Implants; Periodontal Diseases; Autophagy; Odontogenesis; Inflammation
PubMed: 38613351
DOI: 10.1111/jcmm.18297 -
Regenerative Therapy Dec 2024The objective of the present study was to investigate whether NOD-like receptor family pyrin domain-containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes...
OBJECTIVES
The objective of the present study was to investigate whether NOD-like receptor family pyrin domain-containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes pathways were involved in an experimental model of fibroblast activation named nemosis, which was used to mimic circumstances without bacteria stimulation.
METHODS
Nemosis of human dental pulp fibroblast (DPFs) was induced by three-dimensional culture in U-shaped 96-well plates and investigated by scanning electron microscopy (SEM). DPFs monolayers were used as control. Annexin V-FITC/7-AAD apoptosis assay was performed on the DPFs spheroids by flowcytometry. Caspase-1 activity detection assay was conducted on the DPFs spheroids. Quantitative real-time polymerase chain reaction (qRT-PCR), cytokine measurements, Western blot and the effect of COX-2 inhibitor on spheroids was studied.
RESULTS
SEM study observed human dental pulp fibroblast clusters and cell membranes damage on the surface of DPFs spheroids. The percentages of necrotic cells from DPFs spheroids gradually increased as the incubation time increased. A statistically significant increase in caspase-1 activity was observed after DPFs spheroids formation. DPFs spheroids displayed significant amounts of NLRP3, AIM2 mRNA and protein expression, caspase-1 mRNA expression and cleaved Caspase-1 protein expression and high IL-1β concentrations ( < 0.05) than DPFs monolayers. Specific COX-2 inhibitor (NS-398) decreased NLRP3 mRNA and protein expression, cleaved Caspase-1 protein expression, Caspase-1 activity and IL-1β mRNA expression and IL-1β concentrations ( < 0.05). However, Specific COX-2 inhibitor had no impact on AIM2 mRNA and protein expression, caspase-1 mRNA expression and pro-Caspase-1 protein expression.
CONCLUSIONS
In conclusion, clustering human DPFs spontaneously activated NLRP3 and AIM2 inflammasomes and induced IL-1β secretion which could be partially attenuated by COX-2 inhibitor. Thus, nemosis could become a powerful model for studying mechanisms underlying aseptic pulpitis.
PubMed: 38487102
DOI: 10.1016/j.reth.2024.02.010 -
Medicina (Kaunas, Lithuania) Dec 2023Silver diamine fluoride (SDF) has been incorporated into the treatment of dental caries in children, mainly in countries with high caries prevalence. In Europe,...
Silver diamine fluoride (SDF) has been incorporated into the treatment of dental caries in children, mainly in countries with high caries prevalence. In Europe, however, SDF started to gain popularity during the COVID-19 pandemic. This study aimed to investigate the efficacy of SDF and to evaluate dentists'/parents' acceptance of SDF use in paediatric patients treated in a German university setting. A retrospective analysis of all patients treated with SDF between 2017 and 2020 was carried out. Only teeth with no reported clinical/radiographic evidence of irreversible pulpal inflammation were included. The outcome measures were success, minor failures (caries progression, reversible pulpitis) and major failures (irreversible pulpitis, abscess). The treatment acceptance by dentists and the parents of SDF-treated children was cross-sectionally evaluated using questionnaires. Descriptive statistics and Kaplan-Meier survival analysis were performed. A total of 93 patients (mean age 5.3 ± 2.9 years) with 455 treated teeth (418 primary/91.9%; 37 permanent/8.1%) were included and followed up for up to 24 months (19.9 ± 10.5 months). SDF was used for dental caries (98.2%) and hypersensitivity relief on MIH teeth (1.8%). Most teeth did not show any failure (total success 84.2%). A total of 5 teeth (1.1%) showed minor failures, and 67 teeth (14.7%) showed major failures ( = 0.001). Success/failure rates were not affected by patient compliance, gender, dentition, or operator ( > 0.05). In total, 30 questionnaires were collected from parents (mean age 36.8 ± 6.4 years). SDF was applied on anterior ( = 2/6.7%), posterior ( = 15/50%) and anterior/posterior teeth ( = 13/43.3%). At the 1-week follow-up, 80% of parents noticed black teeth discoloration. Treatment satisfaction was higher for posterior (95.2%) than for anterior teeth (36.4%; < 0.001). In the 27 responses from clinicians, SDF was generally considered a viable option in paediatric dentistry ( = 23; 85%). : SDF was found to be effective and well-accepted by parents and dentists for caries inactivation in a paediatric dentistry German university setting.
Topics: Humans; Child; Child, Preschool; Adult; Cariostatic Agents; Cross-Sectional Studies; Pediatric Dentistry; Pulpitis; Dental Caries; Pandemics; Retrospective Studies; Abscess; Quaternary Ammonium Compounds; Fluorides, Topical; Silver Compounds
PubMed: 38276050
DOI: 10.3390/medicina60010016 -
BMC Oral Health Feb 2024Ideally, health services and interventions to improve dental health should be tailored to local target populations. But this is not the standard. Little is known about...
BACKGROUND
Ideally, health services and interventions to improve dental health should be tailored to local target populations. But this is not the standard. Little is known about risk clusters in dental health care and their evaluation based on small-scale, spatial data, particularly among under-represented groups in health surveys. Our study aims to investigate the incidence rates of major oral diseases among privately insured and self-paying individuals in Germany, explore the spatial clustering of these diseases, and evaluate the influence of social determinants on oral disease risk clusters using advanced data analysis techniques, i.e. machine learning.
METHODS
A retrospective cohort study was performed to calculate the age- and sex-standardized incidence rate of oral diseases in a study population of privately insured and self-pay patients in Germany who received dental treatment between 2016 and 2021. This was based on anonymized claims data from BFS health finance, Bertelsmann, Dortmund, Germany. The disease history of individuals was recorded and aggregated at the ZIP code 5 level (n = 8871).
RESULTS
Statistically significant, spatially compact clusters and relative risks (RR) of incidence rates were identified. By linking disease and socioeconomic databases on the ZIP-5 level, local risk models for each disease were estimated based on spatial-neighborhood variables using different machine learning models. We found that dental diseases were spatially clustered among privately insured and self-payer patients in Germany. Incidence rates within clusters were significantly elevated compared to incidence rates outside clusters. The relative risks (RR) for a new dental disease in primary risk clusters were min = 1.3 (irreversible pulpitis; 95%-CI = 1.3-1.3) and max = 2.7 (periodontitis; 95%-CI = 2.6-2.8), depending on the disease. Despite some similarity in the importance of variables from machine learning models across different clusters, each cluster is unique and must be treated as such when addressing oral public health threats.
CONCLUSIONS
Our study analyzed the incidence of major oral diseases in Germany and employed spatial methods to identify and characterize high-risk clusters for targeted interventions. We found that private claims data, combined with a network-based, data-driven approach, can effectively pinpoint areas and factors relevant to oral healthcare, including socioeconomic determinants like income and occupational status. The methodology presented here enables the identification of disease clusters of greatest demand, which would allow implementing more targeted approaches and improve access to quality care where they can have the most impact.
Topics: Humans; Retrospective Studies; Residence Characteristics; Incidence; Spatial Analysis; Socioeconomic Factors; Germany
PubMed: 38331748
DOI: 10.1186/s12903-024-03897-4 -
Journal of Pharmacy & Bioallied Sciences Jul 2023Pain management is a cornerstone in the practice of endodontics. However, optimum pain control has been a challenge in cases of symptomatic irreversible pulpitis...
AIM
Pain management is a cornerstone in the practice of endodontics. However, optimum pain control has been a challenge in cases of symptomatic irreversible pulpitis resulting in a "hot tooth." Thus, the objective of the study is to assess the knowledge and attitude and to determine the clinical protocols of "hot tooth" management followed among general practitioners and specialists.
MATERIALS AND METHODS
The KAP questionnaire contained 05 knowledge, 04 attitudes, and 06 practice-related items. The questionnaire was pretested among 10 randomly selected general dentists and endodontists. Testing-retesting was also performed. The questionnaire was self-administered and the acceptance to answer the questionnaire was considered consent to participate in the study. The sample size was calculated to be 200 with a 95% level of confidence. Descriptive statistics were used. For significance level, < 0.05 was considered statistically significant. The Chi-square test was used for comparison between the endodontists and the general dentists.
RESULTS
The anesthetic techniques that clinicians are most skilled in are infiltration and inferior alveolar nerve block (IANB) - 96.6% and 98.5% respectively. The intraosseous technique (IO) was the least preferred technique (6.8%). The most common supplementary injection used among both the BDS and MDS graduates was intrapulpal anesthesia. In cases of acute pulpitis, 54% of the respondents prescribed NSAIDs as a pre-anesthetic medication.
CONCLUSION
The current study shows that supplemental injections like intraosseous and intraligamental techniques are underutilized. Also, the benefits of preanesthetic medication for hot tooth management are not harnessed among clinicians despite the sufficient body of evidence.
PubMed: 37654287
DOI: 10.4103/jpbs.jpbs_99_23 -
Molecular Pain 2024Toothache is one of the most common types of pain, but the mechanisms underlying pulpitis-induced pain remain unknown. The ionotropic purinergic receptor family (P2X) is...
Toothache is one of the most common types of pain, but the mechanisms underlying pulpitis-induced pain remain unknown. The ionotropic purinergic receptor family (P2X) is reported to mediate nociception in the nervous system. This study aims to investigate the involvement of P2X3 in the sensitisation of the trigeminal ganglion (TG) and the inflammation caused by acute pulpitis. An acute tooth inflammation model was established by applying LPS to the pulp of SD rats. We found that the increased expression of P2X3 was induced by acute pulpitis. A selective P2X3 inhibitor (A-317491) reduced pain-like behavior in the maxillofacial region of rats and depressed the activation of neurons in the trigeminal ganglion induced by pulpitis. The upregulated MAPK signaling (p-p38, p-ERK1/2) expression in the ipsilateral TG induced by pulpitis could also be depressed by the application of the P2X3 inhibitor. Furthermore, the expression of markers of inflammatory processes, such as NF-κB, TNF-α and IL-1β, could be induced by acute pulpitis and deduced by the intraperitoneal injection of P2X3 antagonists. Our findings demonstrate that purinergic P2X3 receptor signaling in TG neurons contributes to pulpitis-induced pain in rats and that P2X3 signaling may be a potential therapeutic target for tooth pain.
Topics: Rats; Animals; Pulpitis; NF-kappa B; Rats, Sprague-Dawley; Pain; Signal Transduction; Inflammation; Receptors, Purinergic P2X3; Trigeminal Ganglion
PubMed: 38325814
DOI: 10.1177/17448069241234451