RESUMEN
Periapical lesions are common pathologies affecting the alveolar bone, often initiated by intraradicular lesions resulting from microbial exposure to dental pulp. These microorganisms trigger inflammatory and immune responses. When endodontic treatment fails to eliminate the infection, periapical lesions persist, leading to bone loss. The RANK/RANKL/OPG pathway plays a crucial role in both the formation and the destruction of the bone. In this study, the objective was to inhibit the RANK/RANKL pathway in vitro within exposed Thp-1 macrophages to endodontic microorganisms, specifically Enterococcus faecalis, which was isolated from root canals of 20 patients with endodontic secondary/persistent infection, symptomatic and asymptomatic, and utilizing an α-IRAK-4 inhibitor, we introduced endodontic microorganisms and/or lipoteichoic acid from Streptococcus spp. to cellular cultures in a culture plate, containing thp-1 cells and/or PBMC from patients with apical periodontitis. Subsequently, we assessed the percentages of RANK+, RANKL+, and OPG+ cells through flow cytometry and measured the levels of several inflammatory cytokines (IL-1ß, TNF-α, IL-6, IL-8, IL-10, and IL-12p70) in the cellular culture supernatant through a CBA kit and performed analysis by flow cytometry. A significant difference was observed in the percentages of RANK+RANKL+, OPG+ RANKL+ cells in thp-1 cells and PBMCs from patients with apical periodontitis. The findings revealed significant differences in the percentages of the evaluated cells, highlighting the novel role of the IRAK-4 inhibitor in addressing this oral pathology, apical periodontitis, where bone destruction is observed.
Asunto(s)
Macrófagos , Periodontitis Periapical , Ligando RANK , Receptor Activador del Factor Nuclear kappa-B , Transducción de Señal , Humanos , Ligando RANK/metabolismo , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Células THP-1 , Receptor Activador del Factor Nuclear kappa-B/metabolismo , Periodontitis Periapical/metabolismo , Periodontitis Periapical/microbiología , Periodontitis Periapical/patología , Citocinas/metabolismo , Enterococcus faecalis , Lipopolisacáridos , Cavidad Pulpar/microbiología , Cavidad Pulpar/metabolismo , Masculino , Osteoprotegerina/metabolismo , Adulto , Ácidos Teicoicos/farmacologíaRESUMEN
OBJECTIVE: To evaluate histologically and radiographically the potential of dog's immature roots with apical periodontitis to regenerate after regenerative endodontic treatment using mesoporous silica nanoparticles (MSNs) with/without bone morphogenic protein (BMP-2) as scaffolds. METHODS: In 4 mongrel dogs, 56 immature teeth with 96 roots were infected, resulting in necrotic pulps and periapical pathosis. According to the evaluation time (Group I = 30 days and Group II = 90 days), 90 roots were divided into two equal groups (45 roots each) and 6 roots used to replace any lost root during the procedure. The two main groups were further divided according to treatment protocol into 5 subgroups (9 roots each): blood clot (BC subgroup), mesoporous silica nanoparticles scaffold only (MSNs subgroup), mesoporous silica nanoparticles impregnated with BMP2 (MSNs + BMP2 subgroup), infected teeth without treatment (+ ve control subgroup) and normal untouched teeth (-ve control subgroup). All teeth surfaces were coated with Tincture iodine and calcium hydroxide was applied prior to treatment protocols. Then, teeth were restored with glass ionomer filling to seal the remaining part of the access cavity. Radiography evaluation of the increase in root length, root thickness and occurrence of apical closure were performed. Following the sacrifice of the two dogs at each time of evaluation, histopathological analysis was performed and included the inflammatory cells count, bone resorption, tissue ingrowth, deposition of hard tissue, and closure of the apical part. All data were statistically analyzed. RESULTS: Compared to BC subgroup, MSNs and MSNs + BMP-2 subgroups exhibited significant higher increase in root length and thickness as well as higher vital tissue in-growth and new hard tissue formation in group II (P < 0.05). MSNs + BMP-2 subgroup had significant higher increase in root length and thickness as well as significant lower inflammatory cell count than MSNs subgroup in both groups (P < 0.05). There were no significant differences between MSNs and MSNs + BMP-2 subgroups regarding new hard tissue formation in both groups and apical closure in group I (P > 0.05). CONCLUSION: MSNs with/without BMP-2 scaffolds enabled the continuing growth of roots in immature teeth with necrotic pulps and periapical pathosis. Addition of BMP-2 to MSNs scaffold improved its outcome in regenerative endodontics. CLINICAL RELEVANCE: MSNs with/without BMP-2 scaffolds may alternate blood clot for regenerative endodontic treatment of immature teeth with necrotic pulps.
Asunto(s)
Pulpa Dental , Nanopartículas , Dióxido de Silicio , Andamios del Tejido , Raíz del Diente , Animales , Perros , Raíz del Diente/efectos de los fármacos , Raíz del Diente/diagnóstico por imagen , Proteína Morfogenética Ósea 2 , Periodontitis Periapical/terapia , Periodontitis Periapical/patología , Necrosis de la Pulpa Dental/terapia , Regeneración/efectos de los fármacos , Endodoncia Regenerativa/métodosRESUMEN
AIM: To elucidate whether mitochondrial biogenesis disorder and damage from oxidative stress promote refractory apical periodontitis (RAP) in rat and human. METHODOLOGY: Twenty Enterococcus faecalis-induced RAPs were established in the maxillary first molars of male Wistar rats. Concurrently, 12 periapical lesion specimens from patients presenting with RAP were obtained by apicoectomy. Radiographic examination and histologic analysis were conducted to evaluate periapical bone tissue destruction and morphological changes. The expression of key regulators of mitochondrial biogenesis, PGC-1α and Nrf2, were detected by immunohistochemistry and double immunofluorescence staining, Western blot and real-time PCR were also assayed. Mitochondrial ROS (mtROS) was identified by MitoSOX staining. Mitochondrial function was detected by the quantification of ATP production, mitochondrial DNA (mtDNA) copy number and activities of mitochondrial respiratory chain complexes. Furthermore, mitochondrial oxidative stress was evaluated by the determination of 3-nitrotyrosine (3-NT), 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxy-deoxyguanosine (8-OHdG) expression levels, as well as malondialdehyde (MDA) expression and antioxidant capacity. Student's t-test was performed to determine significance between the groups; p < .05 was considered significant. RESULTS: In the maxilla, significantly more bone resorption, greater number of periapical apoptotic cells and Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells were observed in the RAP group compared with the control group (p < .01). PGC-1α and Nrf2 were significantly reduced in rat and human RAP lesions compared to the control group (p < .01) at both the mRNA and protein levels. Double immunofluorescence analysis of PGC-1α or Nrf2 with TOMM20 also indicated that mitochondrial biogenesis was impaired in RAP group (p < .01). Additionally, mitochondrial dysfunction was observed in RAP group, as reflected by increased mtROS, decreased ATP production, reduced mtDNA copy number and complexes of the mitochondrial respiratory chain. Finally, the expression levels of mitochondrial oxidative stress markers, 3-NT, 4-HNE and 8-OHdG, were significantly increased in the RAP group (p < .01). Consistent with this, systemic oxidative damage was also present in the progression of RAP, including increased MDA expression and decreased antioxidant activity (p < .01). CONCLUSIONS: Mitochondrial biogenesis disorder and damage from oxidative stress contribute to the development of RAP.
Asunto(s)
Factor 2 Relacionado con NF-E2 , Biogénesis de Organelos , Estrés Oxidativo , Periodontitis Periapical , Ratas Wistar , Periodontitis Periapical/metabolismo , Periodontitis Periapical/patología , Animales , Masculino , Humanos , Ratas , Factor 2 Relacionado con NF-E2/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Mitocondrias/metabolismo , Adulto , ADN Mitocondrial/metabolismo , Modelos Animales de EnfermedadRESUMEN
AIM: Autophagy is involved in human apical periodontitis (AP). However, it is not clear whether autophagy is protective or destructive in bone loss via the receptor activator of nuclear factor-κB ligand (RANKL)/RANK/osteoprotegerin (OPG) axis. This study aimed to investigate the involvement of autophagy via the RANKL/RANK/OPG axis during the development of AP in an experimental rat model. METHODOLOGY: Twenty-four female Sprague-Dawley rats were divided into control, experimental AP (EAP) + saline, and EAP + 3-methyladenine (An autophagy inhibitor, 3-MA) groups. The control group did not receive any treatment. The EAP + saline group and the EAP + 3-MA group received intraperitoneal injections of saline and 3-MA, respectively, starting 1 week after the pulp was exposed. Specimens were collected for microcomputed tomography (micro-CT) scanning, histological processing, and immunostaining to examine the expression of light chain 3 beta (LC3B), RANK, RANKL, and OPG. Data were analysed using one-way analysis of variance (p < .05). RESULTS: Micro-CT showed greater bone loss in the EAP + 3-MA group than in the EAP + saline group, indicated by an elevated trabecular space (Tb.Sp) (p < .05). Inflammatory cell infiltration was observed in the EAP + saline and EAP + 3-MA groups. Compared with EAP + saline group, the EAP + 3-MA group showed weaker expression of LC3B (p < .01) and OPG (p < .05), more intense expression of RANK (p < .01) and RANKL (p < .01), and a higher RANKL/OPG ratio (p < .05). CONCLUSION: Autophagy may exert a protective effect against AP by regulating the RANKL/RANK/OPG axis, thereby inhibiting excessive bone loss.
Asunto(s)
Pérdida de Hueso Alveolar , Autofagia , Modelos Animales de Enfermedad , Osteoprotegerina , Periodontitis Periapical , Ligando RANK , Ratas Sprague-Dawley , Receptor Activador del Factor Nuclear kappa-B , Microtomografía por Rayos X , Animales , Femenino , Ratas , Adenina/análogos & derivados , Adenina/farmacología , Pérdida de Hueso Alveolar/metabolismo , Pérdida de Hueso Alveolar/patología , Osteoprotegerina/metabolismo , Periodontitis Periapical/metabolismo , Periodontitis Periapical/patología , Ligando RANK/metabolismo , Receptor Activador del Factor Nuclear kappa-B/metabolismoRESUMEN
BACKGROUND: Small extracellular vesicles derived from milk (Milk-sEVs) have the advantages of easy availability, low cost, low toxicity, and inhibition of inflammation. CD36 mediates inflammation stress in a variety of disease states. The purpose of this study was to investigate the role of Milk-sEVs in inhibiting fibroblast inflammation through CD36 and provide reference data for the treatment of chronic apical periodontitis. RESULTS: The addition of Milk-sEVs resulted in decreased expression of inflammation-related factors in L929 cells, and transcriptome sequencing screened for the DEG CD36 in the Milk-sEV treatment group under inflammation. The mouse model of apical periodontitis was successfully established, and CD36 expression increased with the development of inflammation. Transfection of si-CD36 into L929 cells reduced inflammation by inhibiting activation of the MAPK signaling pathway. CONCLUSIONS: CD36 expression increased with the development of apical periodontitis. In the setting of LPS-mediated inflammation, Milk-sEVs inhibited activation of the MAPK signaling pathway by decreasing the expression of CD36 in L929 cells and thereby reducing inflammation.
Asunto(s)
Antígenos CD36 , Vesículas Extracelulares , Sistema de Señalización de MAP Quinasas , Leche , Periodontitis Periapical , Animales , Antígenos CD36/metabolismo , Antígenos CD36/genética , Vesículas Extracelulares/metabolismo , Ratones , Leche/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Periodontitis Periapical/metabolismo , Periodontitis Periapical/patología , Línea Celular , Modelos Animales de Enfermedad , Inflamación/metabolismo , Inflamación/patología , MasculinoRESUMEN
Apical periodontitis (AP) is a condition characterized by inflammatory and infectious components in the tooth canal. AP affects periradicular tissues and has systemic repercussions. Physical exercise is a structured activity that requires cardiorespiratory function, and can modulate the inflammatory profile in pathological conditions. As a result, this study aimed to determine the effects of aerobic physical training (PT) on the alveolar bone with and without AP, and its systemic inflammatory repercussions. AP was induced in the mandibular first molars, and PT was performed on a treadmill for five consecutive days over four weeks, with progressive increases in speed and activity time. Blood samples were collected to determine serum cytokine levels using immunoassays, and alveolar bone samples were collected for histopathological evaluation, lesion volume and microarchitecture assessment using computed microtomography. Animals with AP had increased pro-inflammatory cytokines levels compared to those without AP; however, these levels were attenuated or restored by PT. Compared to the AP group, the AP + PT group had a smaller lesion volume and greater preservation of the bone trabeculae in the remaining alveolar bone surrounding the lesion. In overall, PT minimized the severity of AP proving to be a valid strategy for individuals undergoing endodontic treatment.
Asunto(s)
Citocinas , Periodontitis Periapical , Humanos , Animales , Periodontitis Periapical/terapia , Periodontitis Periapical/patología , Ejercicio Físico , Huesos/patologíaRESUMEN
OBJECTIVES: Computed tomography (CT) and cone beam computed tomography (CBCT) represent the main imaging modalities used in rhinosinusitis patients and are also important in odontogenic sinusitis (OS) diagnostics. Reports, however, often lack information on dentition. Here, we aimed to determine how maxillary dentition is initially interpreted in rhinosinusitis patients' CT/CBCT reports and which dental findings in particular are potentially missed, thus needing more attention. STUDY DESIGN: CT/CBCT scans and radiological reports from 300 rhinosinusitis patients were analysed focusing specifically on dental findings. An experienced oral and maxillofacial radiologist re-evaluated the scans and the assessment was compared to the original reports using the McNemar test. RESULTS: From the 300 original reports, 233 (77.7%) mentioned the maxillary teeth. The most frequent statement (126/300, 42.0%) was 'no apical periodontitis'. Apical periodontitis and severe alveolar bone loss were significantly overlooked (p < 0.001). Amongst the 225 patients for whom the CT/CBCT report initially lacked information on dental pathology, 22 patients were diagnosed with apical periodontitis and 16 with severe alveolar bone loss upon re-evaluation. CONCLUSIONS: Dental pathology remains underreported in rhinosinusitis patients' CT/CBCT reports. Because these reports affect OS diagnostics, a routine and structured review of the maxillary teeth by a radiologist is necessary. Such examinations should encompass the maxillary teeth.
Asunto(s)
Tomografía Computarizada de Haz Cónico , Sinusitis , Humanos , Femenino , Masculino , Tomografía Computarizada de Haz Cónico/métodos , Adulto , Sinusitis/diagnóstico por imagen , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Anciano , Adulto Joven , Adolescente , Rinitis/diagnóstico por imagen , Pérdida de Hueso Alveolar/diagnóstico por imagen , Senos Paranasales/diagnóstico por imagen , Senos Paranasales/patología , Anciano de 80 o más Años , Periodontitis Periapical/diagnóstico por imagen , Periodontitis Periapical/patologíaRESUMEN
OBJECTIVE: To explore the pathogenic factors associated with maxillary sinus mucosal thickening with Cone-beam computed Tomography (CBCT). METHODS: From 2016 through 2020, 93 patients with periapical periodontitis or periodontitis in the maxillary posterior dental region were selected. RESULTS: The preoperative thickness of the periodontitis group was significantly higher than that of the periapical periodontitis group (P < 0.05). The difference achieves statistical significance for the comparison of the thickness change with various severity of inflammation (F = 54.824, P = 0.000), the change with time (F = 312.741, P = 0.000). and the change with the interaction severity of inflammation and timeï¼F = 86.132, P = 0.000). CONCLUSIONS: Patients with maxillary sinus mucosa thickening caused by periodontitis and periapical periodontitis should be extracted their infectious teeth and get thoroughly debridement. Maxillary sinus augmentation can perform favorable efforts 3-6 months after extracting teeth.
Asunto(s)
Periodontitis Periapical , Periodontitis , Tomografía Computarizada de Haz Cónico Espiral , Humanos , Seno Maxilar/diagnóstico por imagen , Seno Maxilar/patología , Estudios Retrospectivos , Membrana Mucosa , Periodontitis Periapical/diagnóstico por imagen , Periodontitis Periapical/patología , Periodontitis/diagnóstico por imagen , Periodontitis/patología , Inflamación/patología , Tomografía Computarizada de Haz CónicoRESUMEN
OBJECTIVE: The objectives of this study were to isolate, characterize progenitor cells from blood in the root canals of necrotic immature permanent teeth evoked from periapical tissues and evaluate the applicable potential of these isolated cells in Regenerative Endodontics. DESIGN: Ten necrotic immature permanent teeth from seven patients were included. Evoked bleeding from periapical tissues was induced after chemical instrumentation of the root canals. Cells were isolated from the canal blood and evaluated for cell surface marker expression, multilineage differentiation potential, proliferation ability, and target protein expression. Cell sheets formed from these cells were transferred into human root segments, and then transplanted into nude mice. Histological examination was performed after eight weeks. Data analysis was conducted using one-way ANOVA followed by Tukey's post-hoc comparison, considering p < 0.05 as statistically significant. RESULTS: The isolated cells exhibited characteristics typical of fibroblastic cells with colony-forming efficiency, and displayed Ki67 positivity and robust proliferation. Flow cytometry data demonstrated that at passage 3, these cells were positive for CD73, CD90, CD105, CD146, and negative for CD34 and CD45. Vimentin expression indicated a mesenchymal origin. Under differentiation media specific differentiation media, the cells demonstrated osteogenic, adipogenic, and chondrogenic differentiation potential. Subcutaneous root canals with cell sheets of isolated cells in nude mice showed the formation of pulp-like tissues. CONCLUSIONS: This study confirmed the presence of progenitor cells in root canals following evoked bleeding from periapical tissues of necrotic immature teeth. Isolated cells exhibited similar immunophenotype and regenerative potential with dental mesenchymal stromal cells in regenerative endodontic therapy.
Asunto(s)
Periodontitis Periapical , Endodoncia Regenerativa , Animales , Ratones , Humanos , Tejido Periapical/patología , Necrosis de la Pulpa Dental/terapia , Ratones Desnudos , Periodontitis Periapical/patología , Tratamiento Basado en Trasplante de Células y Tejidos , Tratamiento del Conducto RadicularRESUMEN
BACKGROUND: The present study aimed to evaluate the effectiveness of using platelet-rich fibrin (PRF) as the apical matrix for the placement of MTA in nonsurgical endodontic therapy for teeth with periapical lesions and open apices. METHODS: Twelve teeth from eleven patients with periapical periodontitis and open apices were enrolled in the study. Nonsurgical endodontic therapy was performed with the PRF used as an apical barrier and the MTA manipulated as an apical plug for further thermoplasticized gutta percha in the remaining part of the root canal. Clinical signs and periapical digital radiographs were recorded and analyzed to evaluate the curing progress after periodical follow-ups of 1, 3, and 6 months. The horizontal dimension of the periapical lesion was determined, and the changes in the dimensions were recorded each time. The Friedman test was used for statistical analysis, with P < .05 serving as the threshold for determining statistical significance. RESULTS: All patients had no clinical symptoms after the first month of treatment, with a significant reduction in the periapical lesion after periodical appointments. CONCLUSIONS: PRF is an effective barrier when combined with MTA for the treatment of teeth with periapical periodontitis and open apices.
Asunto(s)
Periodontitis Periapical , Fibrina Rica en Plaquetas , Materiales de Obturación del Conducto Radicular , Humanos , Compuestos de Calcio/uso terapéutico , Materiales de Obturación del Conducto Radicular/uso terapéutico , Gutapercha/uso terapéutico , Periodontitis Periapical/terapia , Periodontitis Periapical/patología , Combinación de Medicamentos , Ápice del Diente/diagnóstico por imagen , Ápice del Diente/patología , Óxidos/uso terapéutico , Silicatos/uso terapéuticoRESUMEN
INTRODUCTION: Dental pulp regeneration is challenging in endodontics. Cellular therapy is an alternative approach to induce dental pulp regeneration. Mesenchymal stromal cells (MSCs) have the capacity to induce dental pulp-like tissue formation. In this study, we evaluated the capacity of allogeneic bone marrow MSCs (BM-MSCs) to regenerate pulp following necrosis and apical periodontitis in children's permanent immature apex teeth. METHODS: Patients aged 8 to 12 years with pulp necrosis and apical periodontitis were evaluated. The study included 15 teeth (13 incisors and 2 molars) from 14 patients (8 boys and 6 girls). Radiographic evaluation showed periapical radiolucency and immature apex teeth. There was no response to cold or electric pulp testing. The root canal of each tooth was cleaned, shaped, and Ca(OH)2 used as an interappointment medication. Cryopreserved allogeneic BM-MSCs were thawed, expanded, incorporated into preclotted platelet-rich plasma, and implanted into the tooth's pulp cavity. They were sealed with bioceramic cement and composite. Sensibility, apical foramen, calcium deposits within the root canal, and resolution of periapical lesions were evaluated in each tooth over the following 12 months. RESULTS: Based on 9 variables established for dental pulp-like tissue regeneration, all MSC-treated teeth showed evidence of successful regeneration. Clinical and radiographic evaluation of the treated teeth showed periapical lesion healing, sensitivity to cold and electricity, decreased width of the apical foramen, and mineralization within the canal space. CONCLUSIONS: Transplantation of allogeneic MSCs induces the formation of dental pulp-like tissue in permanent immature apex teeth with pulp necrosis and apical periodontitis. Implant of MSCs constitutes a potential therapy in regenerative endodontics in pediatric dentistry. Future studies incorporating a larger sample size may confirm these results.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Células Madre Mesenquimatosas , Periodontitis Periapical , Masculino , Femenino , Niño , Humanos , Necrosis de la Pulpa Dental/terapia , Necrosis de la Pulpa Dental/patología , Pulpa Dental/patología , Médula Ósea/patología , Regeneración , Periodontitis Periapical/terapia , Periodontitis Periapical/patología , Tratamiento del Conducto Radicular , Ápice del Diente/patología , Dentina/patologíaRESUMEN
INTRODUCTION: Diet-induced metabolic syndrome may influence the progression and healing of apical periodontitis (AP). The aim of this study was to evaluate the inflammatory immune response of dendritic cells (DCs) and T helper (Th) cells in normal versus obese mice with AP. METHODS: Twenty male C57BL/6 mice were divided into 2 groups: normal chow (NC) and high-fat diet (HFD) for 12 wk. AP was induced in both groups by creating pulp exposure of the right first maxillary molar to the oral environment. Contralateral first molars from each mouse were used as a control. The animal's body mass was recorded on a weekly basis, and they were euthanized after 30 d. The maxillae were removed and processed for micro-computed tomography (micro-CT), histologic analysis, and immunofluorescence staining for DCs (CD11c), Th17 (IL-17A), and T regulatory cells (FOXP3 and IL-10). Different groups were analyzed by Mann-Whitney U test, Student t test, and ordinary 1-way analysis of variance followed by Tukey's multiple comparisons test. The level of significance (α) was set at 0.05. RESULTS: The HFD group showed larger AP lesions than the NC group from micro-CT analysis. For the NC group, induction of AP significantly increased immune cell infiltration when compared with control. HFD showed increased DCs and Th17 infiltration in the control group without AP. In addition, there was no significant change in the amount of DCs and Th17 in the HFD-AP group when compared with the NC-AP and HFD-control groups. CONCLUSIONS: HFD resulted in an increased immune cell infiltration in the periapical area without AP. Despite the larger AP lesion observed in HFD-AP than that of NC-AP, the amount of infiltrated inflammatory cells did not differ significantly. The results of this study suggest that the DCs and Th17 inflammatory pathways are affected by HFD in the periapical region, but their contribution toward AP complicated by metabolic syndrome requires further investigation.
Asunto(s)
Síndrome Metabólico , Periodontitis Periapical , Ratas , Ratones , Masculino , Animales , Ratas Wistar , Dieta Alta en Grasa/efectos adversos , Microtomografía por Rayos X , Ratones Endogámicos C57BL , Periodontitis Periapical/patología , Células Dendríticas/metabolismo , Células Dendríticas/patologíaRESUMEN
BACKGROUND: Application of pulp regenerative cell therapy for mature teeth with periapical lesions is a critical clinical challenge. The bacterial infection in inaccessible location within the root canal system and in the periapical lesions could cause resistance and impediment, leading to limitations in successful therapy. Thus, the aim of this study was to examine the effect of residual bacteria on the outcome of pulp regeneration in mature teeth with apical periodontitis in dogs. METHODS: Periapical lesions were induced in 32 root canals of 4 dogs in two different models in severities, model A and model B. Model A (moderate infection): the canal exposed to the oral cavity for 2 weeks and then closed for 2 weeks. Model B (severe infection): the canal exposed to the oral cavity for 2 months and then closed for 5 months. All root canals were irrigated with 6% sodium hypochlorite, and 3% EDTA and further with 0.015% levofloxacin-containing nanobubbles, which was also used as an intracanal medicament. The aseptic conditions were examined by bacterial anaerobic culture and/or PCR analyses. The root canal treatment was repeated several times, and allogeneic dental pulp stem cells were transplanted into the root canals. The radiographic evaluation of periapical lesions was performed by cone-beam computed tomography before the first treatment, just after cell transplantation, and after 2 months and 6 months in both model A, model B, respectively. The animals were then sacrificed and the jaw blocks were harvested for histological and histobacteriological evaluations of pulp regeneration and periapical tissue healing. Furthermore, the DiI-labelled DPSCs were transplanted into the root canals after complete disinfection (n = 4) or without root canal treatment (n = 4) in the apical periodontitis model (model A) in one dog, and cell localization was compared 72 h after transplantation. RESULTS: In 8 out of 12 canals from model A, and 10 out of 15 canals from model B, pulp regeneration with good vascularization, innervation, and a significant reduction in the radiolucent area of the periapical lesions were observed. However, in the other 4 canals and 5 canals from model A and model B, respectively, no pulp tissue was regenerated, and inflammation in the periapical tissue, and external resorption or healed external resorption were detected. The presence of residual bacteria in the periapical tissues and severe inflammation were significantly associated with inhibition of regenerated pulp tissue in these 9 unsuccessful canals (P < 0.05, each) (OR = 0.075, each) analyzed by multiple logistic regression analysis. For cellular kinetics, transplanted cells remained in the disinfected root canals, while they were not detected in the infected root canals, suggesting their migration through the apical foramen under the influence of inflammation. CONCLUSIONS: A true pulp-dentin complex was regenerated in the root canal by the pulp regenerative therapy in mature teeth with apical lesions. The successful pulp regeneration was negatively associated both with residual bacteria and inflammation in the periapical tissue.
Asunto(s)
Periodontitis Periapical , Materiales de Obturación del Conducto Radicular , Animales , Perros , Pulpa Dental/patología , Desinfección , Materiales de Obturación del Conducto Radicular/uso terapéutico , Regeneración , Periodontitis Periapical/tratamiento farmacológico , Periodontitis Periapical/patología , Bacterias , Inflamación , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
OBJECTIVES: Immunoglobulin (Ig)A nephropathy has been associated with oral infections such as periodontitis, but its pathogenesis is not fully understood; no treatments exist. This study analyzes the influence of IgA nephropathy, an autoimmune disease, on the pathogenesis of pulpitis and apical periodontitis. METHODS: Two groups of mice were used in pulp infection experiments: high serum IgA nephropathy model mice (HIGA) and control mice (BALB/c). Histologic analyses of the pulp and apical periodontal tissues were performed on days 3, 5, 7, 14, and 28 following oral bacterial infection. The dynamics of odontoblasts, apoptotic cells, and IgA expression were analyzed using anti-Nestin, TUNEL, and anti-IgA staining, respectively. RESULTS: Inflammatory cells infiltrated the exposed pulp at day three in both groups and by 14 days, these cells had infiltrated from the pulp to the apical periodontal tissue. The area of necrotic pulp tissue increased significantly in the control group at seven days. Odontoblasts decreased from day three onwards and disappeared by 28 days in both groups. The number of apoptotic cells in the pulp and apical periodontal tissues was significantly higher in the experimental group at day 28. The experimental group exhibited a significant increase in IgA production in the pulp after 14 days. Bone resorption in the apical periodontal tissue was significantly decreased in the experimental group at day 28. CONCLUSIONS: The results of this study suggest that IgA nephropathy may modulate the inflammatory response and sustain long-term biological defense responses in pulpitis and apical periodontitis in HIGA mice.
Asunto(s)
Glomerulonefritis por IGA , Periodontitis Periapical , Pulpitis , Ratones , Animales , Pulpitis/complicaciones , Pulpitis/patología , Glomerulonefritis por IGA/etiología , Glomerulonefritis por IGA/metabolismo , Glomerulonefritis por IGA/patología , Periodontitis Periapical/complicaciones , Periodontitis Periapical/patología , Pulpa Dental/metabolismo , Pulpa Dental/patología , Inmunoglobulina ARESUMEN
Apical periodontitis (AP) is one of the most prevalent disorders in dentistry. However, it can be underdiagnosed in asymptomatic patients. In addition, the perioperative evaluation of 3-dimensional (3D) lesion volume is of great clinical relevance, but the required slice-by-slice manual delineation method is time- and labor-intensive. Here, for quickly and accurately detecting and segmenting periapical lesions (PALs) associated with AP on cone beam computed tomography (CBCT) images, we proposed and geographically validated a novel 3D deep convolutional neural network algorithm, named PAL-Net. On the internal 5-fold cross-validation set, our PAL-Net achieved an area under the receiver operating characteristic curve (AUC) of 0.98. The algorithm also improved the diagnostic performance of dentists with varying levels of experience, as evidenced by their enhanced average AUC values (junior dentists: 0.89-0.94; senior dentists: 0.91-0.93), and significantly reduced the diagnostic time (junior dentists: 69.3 min faster; senior dentists: 32.4 min faster). Moreover, our PAL-Net achieved an average Dice similarity coefficient over 0.87 (0.85-0.88), which is superior or comparable to that of other existing state-of-the-art PAL segmentation algorithms. Furthermore, we validated the generalizability of the PAL-Net system using multiple external data sets from Central, East, and North China, showing that our PAL-Net has strong robustness. Our PAL-Net can help improve the diagnostic performance and speed of dentists working from CBCT images, provide clinically relevant volume information to dentists, and can potentially be applied in dental clinics, especially without expert-level dentists or radiologists.
Asunto(s)
Periodontitis Periapical , Tomografía Computarizada de Haz Cónico Espiral , Humanos , Algoritmos , Redes Neurales de la Computación , Tomografía Computarizada de Haz Cónico , Periodontitis Periapical/diagnóstico por imagen , Periodontitis Periapical/patología , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
OBJECTIVE: To evaluate the effects of cigarette smoke inhalation on the immune-inflammatory profile of experimental apical periodontitis in rats. METHODOLOGY: In total, 32 male Wistar rats were divided into four groups (n = 8): AP-induced apical periodontitis; S-cigarette smoke inhalation; APS-induced AP and cigarette smoke inhalation; and C (control)-neither AP nor cigarette smoke inhalation. To induce cigarette smoke inhalation, the animals were kept in a chamber filled with tobacco smoke for 8 min thrice a day for 50 days. AP was induced 20 days after inhalation initiation by exposing their coronary pulp to their oral environment for 30 days. After animals were euthanized, their right hemimaxillae were removed for histopathological, semi-quantitative and immunohistochemical (F4/80, CD206 and iNOS) analyses. RESULTS: Quantitative data showed a moderate number of inflammatory infiltrates in AP and an intense number in APS (p < .05). Comparing F4/80+ cells showed no statistically significant differences among groups, but we found more CD206+ cells in AP than in C and S (p > .05). INOS+ immunostaining showed a significant increase in AP and APS, when compared with C and S (p < .05). APS had more iNOS+ cells than AP (p < .05). CONCLUSION: Cigarette smoke inhalation worsened AP, leading to a predominantly pro- inflammatory profile in our experimental model.
Asunto(s)
Fumar Cigarrillos , Periodontitis Periapical , Ratas , Masculino , Animales , Ratas Wistar , Periodontitis Periapical/patologíaRESUMEN
Osteoimmune diseases, such as apical periodontitis, are prevalent, often painful, inflammatory conditions resulting in bone loss and reduced quality of life. There is growing evidence that the nociceptive fibers densely innervating affected tissues regulate disease progression; therefore, we hypothesized that nociceptors regulate the transcriptomic profile of the periapical osteolytic lesion in a mouse model of apical periodontitis. Male control and nociceptor-ablated mice underwent pulp exposures, and after 0, 7, or 14 days, total RNA from periapical tissues was submitted for sequencing and bioinformatic analysis. Pulp exposure triggers the differential expression of hundreds of genes over the course of infection. At 14 days post pulp exposure, 422 genes, including Tnf, Il1a, and Il1b, were differentially expressed between nociceptor-ablated and control mice with greater enrichment of biological processes related to inflammation in nociceptor-ablated mice. Nociceptor ablation regulates the transcriptomic profile of periapical lesions in a mouse model of apical periodontitis, shifting the gene expression profile to a greater enrichment of inflammatory genes, suggesting nociceptors play a role in the kinetics of the immune response. This newly uncovered neuro-immune axis and its mechanisms in apical periodontitis can be an important therapeutic target for the treatment of this prevalent disease.
Asunto(s)
Periodontitis Periapical , Transcriptoma , Masculino , Ratones , Animales , Nociceptores/patología , Calidad de Vida , Periodontitis Periapical/patología , Tejido PeriapicalRESUMEN
This study was to investigate the new analysis manner of dental hard tissue change using in vivo micro-computed tomography (CT) in rat. Scanning, registration, analyzing, and presenting method to track longitudinal in vivo micro-CT data on dental hard tissues were validated in murine models: formative, dentin thickness after direct pulp capping with mineral trioxide aggregate; resorptive, development of apical bone rarefaction in apical periodontitis model. Serial in vivo micro-CT scans were analyzed through rigid-registration, active-contouring, deformable-registration, and motion vector-based quantitative analyses. The rate and direction of hard tissue formation after direct pulp capping was datafied by tracing coordinate shift of fiducial points on pulp chamber outline in formative model. The development of apical periodontitis could be monitored with voxel counts, and quantitatively analyzed in terms of lesion size, bone loss, and mineral density in resorptive model. This study supports the application of longitudinal in vivo micro-CT for resorptive- and formative-phase specific monitoring of dental hard tissues.
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Recubrimiento de la Pulpa Dental , Periodontitis Periapical , Ratas , Ratones , Animales , Microtomografía por Rayos X/métodos , Recubrimiento de la Pulpa Dental/métodos , Compuestos de Calcio , Silicatos/farmacología , Minerales , Periodontitis Periapical/patología , Combinación de Medicamentos , Óxidos , Pulpa DentalRESUMEN
Programmed cell death (PCD) has been a research focus for decades and different mechanisms of cell death, such as necroptosis, pyroptosis, ferroptosis, and cuproptosis have been discovered. Necroptosis, a form of inflammatory PCD, has gained increasing attention in recent years due to its critical role in disease progression and development. Unlike apoptosis, which is mediated by caspases and characterized by cell shrinkage and membrane blebbing, necroptosis is mediated by mixed lineage kinase domain-like protein (MLKL) and characterized by cell enlargement and plasma membrane rupture. Necroptosis can be triggered by bacterial infection, which on the one hand represents a host defense mechanism against the infection, but on the other hand can facilitate bacterial escape and worsen inflammation. Despite its importance in various diseases, a comprehensive review on the involvement and roles of necroptosis in apical periodontitis is still lacking. In this review, we tried to provide an overview of recent progresses in necroptosis research, summarized the pathways involved in apical periodontitis (AP) activation, and discussed how bacterial pathogens induce and regulated necroptosis and how necroptosis would inhibit bacteria. Furthermore, the interplay between various types of cell death in AP and the potential treatment strategy for AP by targeting necroptosis were also discussed.
Asunto(s)
Necroptosis , Periodontitis Periapical , Humanos , Apoptosis , Periodontitis Periapical/patología , Proteínas Quinasas/metabolismoRESUMEN
INTRODUCTION: We have previously demonstrated that auxiliary metformin therapy promotes healing of apical periodontitis. Here we aimed to investigate the effects of metformin on osteoblast differentiation and osteoclast formation in cultured cells and rat apical periodontitis. METHODS: Murine pre-osteoblasts MC3T3-E1 and macrophages RAW264.7 were cultured under hypoxia (2% oxygen) or normoxia (21% oxygen) and stimulated with receptor activator of nuclear factor-κB ligand (RANKL) when indicated. Metformin was added to the cultures to evaluate its anti-hypoxic effects. Expressions of osteoblast differentiation regulator runt-related transcription factor 2 (RUNX2), RANKL, and osteoclast marker tartrate-resistant acid phosphatase (TRAP) were assessed by Western blot. Apical periodontitis was induced in mandibular first molars of 10 Sprague-Dawley rats. Root canal therapy with or without metformin supplement was performed. Periapical bone resorption was measured by micro-computed tomography. Immunohistochemistry was used to examine RUNX2, RANKL, and TRAP expressions. RESULTS: Hypoxia suppressed RUNX2 expression and enhanced RANKL synthesis in pre-osteoblasts. TRAP production increased in macrophages after hypoxia and/or RANKL stimulation. Metformin reversed hypoxia-induced RUNX2 suppression and RANKL synthesis in pre-osteoblasts. Metformin also inhibited hypoxia and RANKL-enhanced TRAP synthesis in macrophages. Intracanal metformin diminished bone loss in rat apical periodontitis. Comparing with vehicle control, cells lining bone surfaces in metformin-treated lesions had significantly stronger expression of RUNX2 and decreased synthesis of RANKL and TRAP. CONCLUSIONS: Alleviation of bone resorption by intracanal metformin was associated with enhanced osteoblast differentiation and diminished osteoclast formation in rat apical periodontitis. Our results endorsed the role of metformin as an effective medicament for inflammatory bone diseases.