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Inflammation Feb 2024Leukemia inhibitory factor (LIF) has been recognized as a novel inflammatory modulator in inflammation-associated diseases. This study aimed to investigate the...
Leukemia inhibitory factor (LIF) has been recognized as a novel inflammatory modulator in inflammation-associated diseases. This study aimed to investigate the modulation of LIF in dental pulp inflammation. Experimental pulpitis was established in wild-type (WT) and Lif-deficient (Lif) mice. Histological and immunostaining analyses were conducted to assess the role of LIF in the progression of pulpitis. Mouse macrophage cell line (RAW264.7) was treated with LPS to simulate an inflammatory environment. Exogenous LIF was added to this system to examine its modulation in macrophage inflammatory response in vitro. Primary bone marrow-derived macrophages (BMDMs) from WT and Lif mice were isolated and stimulated with LPS to confirm the effect of Lif deletion on macrophage inflammatory response. Supernatants from LIF and LPS-treated human dental pulp cells (hDPCs) were collected and added to macrophages. Macrophage chemotaxis was assessed using transwell assays. The results showed an increased expression of LIF and LIFR with the progression of pulpitis, and LIFR was highly expressed in macrophages. Lif deficiency alleviated experimental pulpitis with the reduction of pro-inflammatory cytokines and macrophage infiltration. Exogenous LIF promoted inflammatory response of LPS-induced macrophages through a STAT3/p65-dependent pathway. Consistently, Lif deletion inhibited macrophage inflammatory response in vitro. Supernatants of LIF-treated hDPCs enhanced macrophage migration in LPS-induced inflammatory environment. Our findings demonstrated that LIF aggravates pulpitis by promoting macrophage inflammatory response through a STAT3/p65-dependent pathway. Furthermore, LIF plays a crucial role in driving the recruitment of macrophages to inflamed pulp tissue by promoting chemokine secretion in DPCs.
Topics: Animals; Humans; Mice; Dental Pulp; Inflammation; Leukemia Inhibitory Factor; Lipopolysaccharides; Macrophages; Pulpitis
PubMed: 37782452
DOI: 10.1007/s10753-023-01910-6 -
International Endodontic Journal Jul 2023To comparatively analyse the levels of culturable bacteria, endotoxins (LPS), tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and substance P in teeth...
Quantitative analysis of culturable bacteria, levels of endotoxins, inflammatory mediators and substance P in teeth with symptomatic irreversible pulpitis and in teeth with vital normal pulp tissues.
AIM
To comparatively analyse the levels of culturable bacteria, endotoxins (LPS), tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and substance P in teeth with symptomatic irreversible pulpitis (SIP) and vital normal pulp (VNP) tissues.
METHODOLOGY
Thirty-two patients were included (20 teeth with SIP and 12 teeth with VNP tissues) in this cross-sectional study. Samples were collected from the full length of the root canals (microbial analysis) and periapical tissues (2 mm beyond the apex for immunological analysis), using sterile absorbent paper points. The levels of culturable bacteria (culture method), endotoxins (LAL Pyrogent 5000), TNF-α, IL-1β and substance P (ELISA) were assessed. The Mann-Whitney test was used for comparisons between the levels of CFU/mL, LPS, TNF-α, IL-1β and substance P in the SIP and VNP groups. The statistical analysis was performed with the significance level set at 5%.
RESULTS
Culturable bacteria were recovered from all teeth with SIP. On the other hand, no positive cultures were observed in the VNP tissues group (p > .05). The levels of LPS were approximately four times higher in teeth with SIP than in teeth with VNP tissues (p < .05). Higher levels of TNF-α and substance P were detected in teeth with SIP (p < .05). On the other hand, no difference in the levels of IL-1β was detected between the two groups (p > .05).
CONCLUSION
Teeth with symptomatic irreversible pulpitis present higher levels of culturable bacteria, endotoxins, TNF-α and substance P than those with vital normal pulp tissues. On the other hand, the levels of IL-1β were similar in teeth from both groups suggesting reduced implications of this inflammatory mediator in the early stages of infection.
Topics: Humans; Pulpitis; Substance P; Endotoxins; Lipopolysaccharides; Inflammation Mediators; Tumor Necrosis Factor-alpha; Cross-Sectional Studies; Dental Pulp; Bacteria
PubMed: 37070606
DOI: 10.1111/iej.13922 -
Biochemical and Biophysical Research... Jul 2024Pulpitis constitutes a significant challenge in clinical management due to its impact on peripheral nerve tissue and the persistence of chronic pain. Despite its...
Pulpitis constitutes a significant challenge in clinical management due to its impact on peripheral nerve tissue and the persistence of chronic pain. Despite its clinical importance, the correlation between neuronal activity and the expression of voltage-gated sodium channel 1.7 (Nav1.7) in the trigeminal ganglion (TG) during pulpitis is less investigated. The aim of this study was to examine the relationship between experimentally induced pulpitis and Nav1.7 expression in the TG and to investigate the potential of selective Nav1.7 modulation to attenuate TG abnormal activity associated with pulpitis. Acute pulpitis was induced at the maxillary molar (M1) using allyl isothiocyanate (AITC). The mice were divided into three groups: control, pulpitis model, and pulpitis model treated with ProTx-II, a selective Nav1.7 channel inhibitor. After three days following the surgery, we conducted a recording and comparative analysis of the neural activity of the TG utilizing in vivo optical imaging. Then immunohistochemistry and Western blot were performed to assess changes in the expression levels of extracellular signal-regulated kinase (ERK), c-Fos, collapsin response mediator protein-2 (CRMP2), and Nav1.7 channels. The optical imaging result showed significant neurological excitation in pulpitis TGs. Nav1.7 expressions exhibited upregulation, accompanied by signaling molecular changes suggestive of inflammation and neuroplasticity. In addition, inhibition of Nav1.7 led to reduced neural activity and subsequent decreases in ERK, c-Fos, and CRMP2 levels. These findings suggest the potential for targeting overexpressed Nav1.7 channels to alleviate pain associated with pulpitis, providing practical pain management strategies.
Topics: Animals; NAV1.7 Voltage-Gated Sodium Channel; Mice; Male; Pulpitis; Trigeminal Ganglion; Neurons; Nerve Tissue Proteins; Proto-Oncogene Proteins c-fos; Voltage-Gated Sodium Channel Blockers; Disease Models, Animal; Intercellular Signaling Peptides and Proteins
PubMed: 38718567
DOI: 10.1016/j.bbrc.2024.150044 -
International Endodontic Journal Dec 2023This study aimed to compare the outcome of SCR and Pulpotomy in teeth with deep caries extending at least 75% into dentine. (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
This study aimed to compare the outcome of SCR and Pulpotomy in teeth with deep caries extending at least 75% into dentine.
METHODOLOGY
This two-armed, parallel-group, randomized, superiority trial included vital mature permanent teeth with deep primary or secondary caries diagnosed radiographically as being at least 75% into the thickness of dentine, without clinical signs of symptomatic irreversible pulpitis or radiographic evidence of a periapical lesion. Carious teeth were blindly allocated to receive either SCR or Pulpotomy using computer-generated randomized patient codes concealed in opaque envelopes. All teeth were reviewed clinically and radiographically at 6 months and 1 year post-treatment. Using a significance level of p < .05, the log rank test and Cox proportional hazards regression were used to compare the outcome of SCR and Pulpotomy and to identify potential prognostic factors, respectively.
RESULTS
In all, 58 teeth in the SCR group and 55 teeth in the pulpotomy group completed treatment, after excluding 6 teeth because they did not complete the allocated treatment and another due to severe periodontal disease. At one year, 57/58 (98.3%) teeth from the SCR group and 48/55 (87.3%) teeth from the Pulpotomy group were available for analysis. One tooth in the Pulpotomy group (2.1%) and eight teeth in the SCR group (14.0%) required the further intervention of root canal treatment (p < .05). There were no other significant prognostic factors for survival. Overall, 91.4% of teeth treated with either SCR or Pulpotomy survived without requiring further intervention over a period of one year. No other adverse events occurred over the review period.
CONCLUSION
Within the limitations of this study, Pulpotomy fares better than SCR in preserving the remaining pulp and periapical health. As a treatment modality, Pulpotomy carries greater cost outlay to patient and takes a longer time to complete treatment than SCR. Long-term follow-up is needed to study the pulpal and restorative outcomes of Pulpotomy and SCR.
Topics: Humans; Pulpotomy; Dental Caries Susceptibility; Pilot Projects; Calcium Compounds; Treatment Outcome; Pulpitis; Dental Caries; Silicates
PubMed: 37795835
DOI: 10.1111/iej.13978 -
Journal of Veterinary Dentistry Sep 2023Microscopic alterations in the dental pulp of dogs have not been extensively studied. The aim of this study was to investigate microscopic alterations of the dental pulp...
Microscopic alterations in the dental pulp of dogs have not been extensively studied. The aim of this study was to investigate microscopic alterations of the dental pulp in dogs' teeth. One hundred and ten surgically extracted teeth (20 incisors, 23 canines, 28 premolars, and 39 molars) from 74 dogs, of different ages, with a history of chronic periodontitis (66 dogs), periapical abscesses (2 dogs), pulpitis (2 dogs), oral cavity neoplasms (2 dogs), dens invaginatus (1 dog), and dental fractures (1 dog) were included. Eight-one maxillary and 29 mandibular teeth were included. Coronal, radicular, and coronal plus radicular calculus were present in 28.2%, 17.3%, and 54.5% of the teeth, respectively. In total 78 teeth (71%) had pulp alterations, including fibrosis (26%), calcification (14%), necrosis associated with the absence of odontoblasts (14%), presence of predentin and dentin inside the cavity (8%), odontoblastic hyperplasia (3%), pigmentation (3%), pulpitis (2%), and pulp stones (1%). Forty-nine (60.5%) of the maxillary teeth and all of the mandibular teeth had pulp alterations. The premolars were most affected, and the molars least affected, by pulp alterations. Pulp fibrosis, calcification, and necrosis were observed in teeth irrespective of the distribution of dental calculus.
Topics: Dogs; Animals; Dental Pulp; Pulpitis; Necrosis; Dental Caries; Fibrosis; Dog Diseases
PubMed: 36814404
DOI: 10.1177/08987564231156507 -
International Endodontic Journal Oct 2023To assess the clinical and radiographic outcome of partial pulpotomy by comparing MTA Angelus and Total Fill BC, as pulpotomy agents, in mature teeth with deep caries... (Randomized Controlled Trial)
Randomized Controlled Trial
Treatment outcome of partial pulpotomy using two different calcium silicate materials in mature permanent teeth with symptoms of irreversible pulpitis: A randomized clinical trial.
AIM
To assess the clinical and radiographic outcome of partial pulpotomy by comparing MTA Angelus and Total Fill BC, as pulpotomy agents, in mature teeth with deep caries and symptoms indicative of irreversible pulpitis.
METHODOLOGY
The study was designed as a parallel-two arm, double-blind, randomized superiority clinical trial registered at www.
CLINICALTRIALS
gov (NCT04870398). Symptomatic mature permanent teeth with deep caries fulfilling the inclusion criteria were randomly treated using either MTA Angelus or Total Fill BC. A partial pulpotomy was performed and following complete haemostasis, the capping material was placed over the remaining pulp tissue and a postoperative periapical radiograph was taken. Clinical and radiographic follow-up evaluation was performed for a median time of 2 years, whereas levels of pain intensity were evaluated preoperatively and for 7 days after intervention using Visual Analogue Scale. For the primary outcome (failure/success of treatment), the Kaplan-Meier survival curves for the capping materials were plotted and a log-rank test for equality of survivor functions was applied. A multivariable random effects Cox Regression model was also applied. For the secondary outcome (postoperatively reported pain), a multivariable mixed effects ordinal logistic regression was structured.
RESULTS
One hundred and thirty-seven teeth in 123 patients underwent partial pulpotomy using randomly either MTA Angelus (N = 74) or Total Fill BC (n = 63). The percentage failure for MTA Angelus and Total Fill BC was 10.8% (8/74) and 17.5% (11/63), respectively, but the difference was not statistically significant [adjusted HR: 1.83; 95% confidence interval (CI): 0.68, 4.91; p = .23]. Weak evidence was found that secondary caries involvement may impose a 3.54 times greater hazard for treatment failure (adjusted HR: 3.54; 95% CI: 1.00, 12.51; p = .05). For each passing minute of procedural bleeding control, there was also a 57% higher hazard for treatment failure (adjusted HR: 1.57; 95% CI: 0.99, 2.48; p = .05). The odds for higher postoperative pain were 4.73 times greater for the Total Fill BC compared to MTA Angelus (adjusted OR: 4.73; 95% CI: 2.31, 9.66; p < .001).
CONCLUSIONS
Both materials exhibited similar and favourable outcome rates after partial pulpotomy in teeth with deep caries and symptoms of irreversible pulpitis. Total Fill BC was associated with a higher level of postoperative pain intensities.
Topics: Humans; Pulpitis; Pulpotomy; Calcium Compounds; Silicates; Oxides; Treatment Outcome; Drug Combinations; Aluminum Compounds
PubMed: 37452640
DOI: 10.1111/iej.13955 -
International Endodontic Journal Jul 2023Pyroptosis is a type of inflammatory cell death and is related to pulpitis and apical periodontitis. In this study, the aim was to investigate how periodontal ligament...
AIM
Pyroptosis is a type of inflammatory cell death and is related to pulpitis and apical periodontitis. In this study, the aim was to investigate how periodontal ligament fibroblasts (PDLFs) and dental pulp cells (DPCs) respond to pyroptotic stimuli and explore whether dimethyl fumarate (DMF) could block pyroptosis in PDLFs and DPCs.
METHODOLOGY
Three methods (stimulation with lipopolysaccharide [LPS] plus nigericin, poly(dA:dT) transfection and LPS transfection) were used to induce pyroptosis in PDLFs and DPCs, two types of fibroblasts related to pulpitis and apical periodontitis. THP-1 cell was used as a positive control. Afterwards, PDLFs and DPCs were treated with or without DMF before inducing pyroptosis to examine the inhibitory effect of DMF. Pyroptotic cell death was measured by lactic dehydrogenase (LDH) release assays, cell viability assays, propidium iodide (PI) staining and flow cytometry. The expression levels of cleaved gasdermin D N-terminal (GSDMD NT), caspase-1 p20, caspase-4 p31 and cleaved PARP were examined by immunoblotting. Immunofluorescence analysis was used to detect the cellular distribution of GSDMD NT.
RESULTS
Periodontal ligament fibroblasts and DPCs were more sensitive to cytoplasmic LPS-induced noncanonical pyroptosis than to canonical pyroptosis induced by stimulation with LPS priming plus nigericin or by poly(dA:dT) transfection. In addition, treatment with DMF attenuated cytoplasmic LPS-induced pyroptotic cell death in PDLFs and DPCs. Mechanistically, it was shown that the expression and plasma membrane translocation of GSDMD NT were inhibited in DMF-treated PDLFs and DPCs.
CONCLUSIONS
This study indicates that PDLFs and DPCs are more sensitive to cytoplasmic LPS-induced noncanonical pyroptosis and that DMF treatment blocks pyroptosis in LPS-transfected PDLFs and DPCs by targeting GSDMD, suggesting DMF might be a promising drug for the management of pulpitis and apical periodontitis.
Topics: Humans; Lipopolysaccharides; Pyroptosis; Dimethyl Fumarate; Pulpitis; Periodontal Ligament; Dental Pulp; Nigericin; Fibroblasts; Periapical Periodontitis
PubMed: 37102402
DOI: 10.1111/iej.13926 -
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 -
Biomolecules Mar 2024Pulpitis is a common and frequent disease in dental clinics. Although vital pulp therapy and root canal treatment can stop the progression of inflammation, they do not... (Review)
Review
Pulpitis is a common and frequent disease in dental clinics. Although vital pulp therapy and root canal treatment can stop the progression of inflammation, they do not allow for genuine structural regeneration and functional reconstruction of the pulp-dentin complex. In recent years, with the development of tissue engineering and regenerative medicine, research on stem cell-based regenerative endodontic therapy (RET) has achieved satisfactory preliminary results, significantly enhancing its clinical translational prospects. As one of the crucial paracrine effectors, the roles and functions of exosomes in pulp-dentin complex regeneration have gained considerable attention. Due to their advantages of cost-effectiveness, extensive sources, favorable biocompatibility, and high safety, exosomes are considered promising therapeutic tools to promote dental pulp regeneration. Accordingly, in this article, we first focus on the biological properties of exosomes, including their biogenesis, uptake, isolation, and characterization. Then, from the perspectives of cell proliferation, migration, odontogenesis, angiogenesis, and neurogenesis, we aim to reveal the roles and mechanisms of exosomes involved in regenerative endodontics. Lastly, immense efforts are made to illustrate the clinical strategies and influencing factors of exosomes applied in dental pulp regeneration, such as types of parental cells, culture conditions of parent cells, exosome concentrations, and scaffold materials, in an attempt to lay a solid foundation for exploring and facilitating the therapeutic strategy of exosome-based regenerative endodontic procedures.
Topics: Regenerative Endodontics; Exosomes; Dental Pulp; Regeneration; Regenerative Medicine
PubMed: 38540750
DOI: 10.3390/biom14030330 -
Archives of Oral Biology Mar 2024Hypoxia-inducible factor-1α (HIF-1α) and its downstream factor, 19 kDa BCL-2 interacting protein 3 (BNIP3), promote cellular autophagy under hypoxic conditions....
OBJECTIVE
Hypoxia-inducible factor-1α (HIF-1α) and its downstream factor, 19 kDa BCL-2 interacting protein 3 (BNIP3), promote cellular autophagy under hypoxic conditions. However, their roles in pulpitis are unclear. Therefore, the changes in inflammatory response and autophagy levels caused by hypoxia during pulpitis were evaluated. Additionally, the regulatory mechanism of HIF-1α/BNIP3 in cellular autophagy in pulpitis was explored.
DESIGN
Pulp from dental pulp tissues of healthy individuals and patients with pulpitis (n = 10) were exposed and combined with a low oxygen simulation chamber to construct pulpitis (n = 6), hypoxia (n = 6), and hypoxia+pulpitis (n = 6) rat models. Hematoxylin and eosin and immunohistochemical staining were used to detect the localization and expression levels of HIF-1α, BNIP3, and autophagy marker protein, LC3B. Transmission electron microscopy was used to confirm autophagosome formation. An in vitro hypoxic model of human dental pulp cells was established, and HIF-1α chemical inhibitor 3-(5'-hydroxymethyl-2'-furyl)- 1-benzylindazole (YC-1) was administered. Immunofluorescence and western blotting were used to detect the localization and protein levels of HIF-1α, BNIP3, and LC3B.
RESULTS
Autophagy is significantly increased and HIF-1α and BNIP3 are elevated in inflamed dental pulp tissue. Both pulp exposure and hypoxia intervention cause inflammatory reactions in rat dental pulp tissue, accompanied by the autophagy activation. Hypoxia significantly enhances HIF-1α/BNIP3 and autophagy activation. BNIP3 downregulates and autophagy reduces after treatment with YC-1.
CONCLUSIONS
In pulpitis, activation of the HIF-1α/BNIP3 signaling pathway driven by hypoxia leads to increased autophagy. This provides a new molecular explanation for autophagy activation in apical periodontitis and new insights into the pathogenesis of the disease.
Topics: Animals; Humans; Rats; Autophagy; Cell Hypoxia; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Membrane Proteins; Mitochondrial Proteins; Proto-Oncogene Proteins; Pulpitis
PubMed: 38199116
DOI: 10.1016/j.archoralbio.2024.105881