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1.
J Endod ; 45(11): 1279-1295.e3, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31542282

RESUMEN

INTRODUCTION: Apical periodontitis (AP), except for the local known consequences, may also be a systemic burden. Circulating inflammatory mediators that are released to sustain the AP lesion can in theory harm other bodily tissues. The aim of this systematic review was to summarize the existing evidence on the influence of AP on the peripheral blood levels of inflammatory mediators and markers of systemic stress. METHODS: A search of MEDLINE-PubMed, Embase, and Cochrane was conducted up to and including February 2019 to identify studies in 5 different languages. The Newcastle-Ottawa Scale was used for quality assessment of the included studies. RESULTS: Twelve of the 20 included studies were case-control studies, and 8 were intervention studies. The data of all the included studies were analyzed descriptively, whereas the data of 11 studies were available for meta-analyses. The study designs were heterogeneous. Nevertheless, the meta-analyses revealed statistically significant differences in C-reactive protein, interleukin 6, and asymmetric dimethylarginine levels between AP subjects and controls in peripheral blood. In addition, the concentration of C3 complement fragment in peripheral blood was significantly lower after the treatment and resolution of AP than before. CONCLUSIONS: The existing literature indicates that AP adds on to systemic inflammation by elevating C-reactive protein, interleukin 6, asymmetric dimethylarginine, and C3 levels. In order to overcome the issue of large variation between study designs, future studies should have clear inclusion criteria, preferably larger cohorts, adequate follow-up of all subjects, and a thorough presentation of the data to enable further exploration of the possible burden of AP on general human health. Nevertheless, there is now stronger evidence that AP contributes to low-grade systemic inflammation.


Asunto(s)
Mediadores de Inflamación , Inflamación , Periodontitis Periapical , Proteína C-Reactiva , Humanos , Mediadores de Inflamación/metabolismo , Interleucina-6/metabolismo , Periodontitis Periapical/inmunología , Periodontitis Periapical/metabolismo
2.
Mediators Inflamm ; 2019: 8767529, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31427888

RESUMEN

Chronic apical periodontitis is characterized by alveolar bone absorption in the apical region and is the result of the participation of various inflammatory mediators. Studies have shown that the Bruton tyrosine kinase- (Btk-) phospholipase Cγ2 (PLCγ2) signaling pathway plays an important role in bone absorption, but it is unknown whether it plays a role in apical periodontitis bone destruction. Therefore, this study verified the role of Btk and PLCγ2 in bone resorption of apical periodontitis by in vivo and in vitro experiments. In the in vivo experiment, a mice model of apical periodontitis was established; apical bone resorption was confirmed by the numbers of osteoclasts and HE staining. Btk, PLCγ2, and nuclear factor of activated T-cells 1 (NFATc-1) were detected by immunohistochemical staining. In the in vitro experiment, lipopolysaccharides (LPS) were used to stimulate osteoclast precursor cell RAW264.7 to establish an inflammatory microenvironment and detect osteoclast differentiation. By silencing Btk, the expression of Btk, PLCγ2, and NFATc-1 was detected by real-time qPCR and Western blot, and osteoclastogenesis was detected by enzyme histochemical staining to further confirm the role of Btk in bone resorption. It was found that the expression of Btk, PLCγ2, and NFATc-1 changed significantly with the progression of inflammation and bone destruction, indicating that Btk and PLCγ2 may be involved in the progression of inflammation in apical periodontitis and bone absorption. In vitro experiments confirmed that the differentiation of osteoclasts and the expression of PLCγ2 and NFATc-1 were significantly inhibited after silencing Btk expression, but osteoclast precursor cells could be differentiated due to the proinflammatory factor lipopolysaccharide. This study demonstrates that Btk and PLCγ2 are key factors involved in the apical inflammatory response and bone destruction.


Asunto(s)
Agammaglobulinemia Tirosina Quinasa/metabolismo , Periodontitis Periapical/metabolismo , Fosfolipasa C gamma/metabolismo , Animales , Resorción Ósea/metabolismo , Diferenciación Celular/fisiología , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Osteoclastos/metabolismo , Osteoclastos/fisiología , Células RAW 264.7 , Transducción de Señal/fisiología
3.
J Endod ; 45(7): 890-897, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31153660

RESUMEN

INTRODUCTION: The aim was to assess the association of inducible costimulator (ICOS) and ICOS ligand with bone destruction in apical periodontitis (AP). METHODS: Specimens from patients presenting with AP were obtained during apicoectomy and subjected to histopathologic analysis and molecular assessment of ICOS/ICOS ligand. In addition, the experimental AP was induced by exposing the pulp of first mandibular molars of rats. Histologic and radiographic examinations were performed to validate the periapical lesions. The immunolocalization and messenger RNA expression of ICOS/ICOS ligand were evaluated by immunofluorescence staining and quantitative real-time polymerase chain reaction. The osteoclastic activities in periapical lesions, including the lesion size and the expression of tartrate-resistant acid phosphatase and the receptor activator of nuclear factor kappa B ligand, were recorded and followed by correlation analysis with ICOS/ICOS ligand expression. RESULTS: In excisional specimens from AP patients, a significantly increased expression of ICOS/ICOS ligand was found compared with the healthy control. In the experimental AP samples, the expression of ICOS/ICOS ligand, tartrate-resistant acid phosphatase, and receptor activator of nuclear factor kappa B ligand was significantly elevated in inflamed periapical tissues (AP group) when compared with the healthy control. The number of ICOS+/ICOS ligand+ cells was highly correlated with the periapical lesion size (r = 0.892, P < .01 and r = 0.930, P < .01, respectively). CONCLUSIONS: The increased expression of ICOS/ICOS ligand in periapical lesions was associated with the inflammatory infiltration and alveolar bone destruction of AP.


Asunto(s)
Pérdida de Hueso Alveolar , Proteína Coestimuladora de Linfocitos T Inducibles , Inflamación , Periodontitis Periapical , Animales , Humanos , Proteína Coestimuladora de Linfocitos T Inducibles/metabolismo , Ligandos , Osteoclastos , Periodontitis Periapical/metabolismo , Tejido Periapical , Proteínas , Ratas , Fosfatasa Ácida Tartratorresistente
4.
J Endod ; 45(8): 1009-1015, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31227229

RESUMEN

INTRODUCTION: The aim of this study was to evaluate the inflammatory profile of T helper (Th) cells in normoglycemic (N) and diabetic rats with apical periodontitis (AP). METHODS: Twenty male Wistar rats were divided in 2 groups: N rats and rats with diabetes mellitus (DM). DM was induced using streptozotocin, and AP was induced by dental pulp exposure of the first mandibular molar to the oral environment. After 30 days, the mandibles were removed and processed for histologic analysis, bacterial analysis, and immunochemical assays for interleukin (IL)-6, tumor necrosis factor alpha, IL-17, IL-23, interferon gamma, and IL-10. The Mann-Whitney U test and Student t test were used for statistical analysis (P < .05). RESULTS: The DM group showed more intense inflammatory infiltrate with larger sizes of bone reabsorption and a greater presence of bacteria than the N group (P < .05). Proinflammatory cytokine levels in the DM group were also greater than those in the N group (P < .05). However, interferon gamma was more intense in the N group than in the DM group (P < .05). CONCLUSIONS: The inflammatory profile of AP in DM is different from that in the N group, suggesting that Th1 is a secondary strain and the Th17 strain is predominant in DM.


Asunto(s)
Diabetes Mellitus Experimental , Periodontitis Periapical , Linfocitos T Reguladores , Células TH1 , Células Th17 , Células Th2 , Animales , Humanos , Inflamación , Masculino , Periodontitis Periapical/metabolismo , Ratas , Ratas Wistar
5.
Mediators Inflamm ; 2019: 8325380, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31011287

RESUMEN

RANKL, a bone-destructive cytokine, and OPG, its osteoprotective counterpart, are expressed in periapical lesions (PLs), which represent hystopatological manifestations of apical periodontitis. However, their regulation in PLs has not been elucidated yet. Therefore, our aim was to study the production of RANKL and OPG and their modulation by pro- and anti-inflammatory cytokines in PL cell cultures. Isolated PL cells were cultured alone or with addition of TNF-α, IFN-ϒ, IL-17, IL-4, IL-10, and IL- 33, respectively. The levels of RANKL and OPG in supernatants were measured by ELISA. The proportion of CD3+ (T cells) and CD19+/CD138+ (B cells/plasma cells) within isolated PLs was determined by immunocytochemistry. The levels of RANKL were higher in cultures of symptomatic PLs compared to asymptomatic PLs and PLs with the dominance of T cells (T-type lesions) over B cells/plasma cells (B-type lesions). A higher proportion of osteodestructive processes (RANKL/OPG ratio > 1.0) were detected in symptomatic PLs. The production of RANKL was upregulated by IFN-ϒ and IL-17 and higher concentrations of IL-33. IL-10 and lower concentrations of IL-33 augmented the production of OPG. The addition of either RANKL or anti-RANKL antibody to the cultures did not modify significantly the production of OPG. In conclusion, this original PL cell culture model suggests that increased bone destruction through upregulated production of RANKL could be associated with exacerbation of inflammation in PLs with the predominance of Th1 and Th17 responses and increased secretion of IL-33. In contrast, IL-10 and lower levels of IL-33, through upregulation of OPG, may suppress osteolytic processes.


Asunto(s)
Citocinas/metabolismo , Osteoprotegerina/metabolismo , Periodontitis Periapical/metabolismo , Ligando RANK/metabolismo , Receptor Activador del Factor Nuclear kappa-B/metabolismo , Adulto , Anciano , Células Cultivadas , Humanos , Inmunohistoquímica , Interleucina-17/metabolismo , Persona de Mediana Edad , Adulto Joven
6.
J Immunol ; 202(7): 2035-2043, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30737274

RESUMEN

Locally produced osteoclastogenic factor RANKL plays a critical role in the development of bone resorption in periradicular periodontitis. However, because RANKL is also required for healthy bone remodeling, it is plausible that a costimulatory molecule that upregulates RANKL production in inflammatory periradicular periodontitis may be involved in the pathogenic bone loss processes. We hypothesized that macrophage migration inhibitory factor (MIF) would play a role in upregulating the RANKL-mediated osteoclastogenesis in the periradicular lesion. In response to pulp exposure, the bone loss and level of MIF mRNA increased in the periradicular periodontitis, which peaked at 14 d, in conjunction with the upregulated expressions of mRNAs for RANKL, proinflammatory cytokines (TNF-α, IL-6, and IL-1ß), chemokines (MCP-1 and SDF-1), and MIF's cognate receptors CXCR4 and CD74. Furthermore, expressions of those mRNAs were found significantly higher in wild-type mice compared with that of MIF-/- mice. In contrast, bacterial LPS elicited the production of MIF from ligament fibroblasts in vitro, which, in turn, enhanced their productions of RANKL and TNF-α. rMIF significantly upregulated the number of TRAP+ osteoclasts in vitro. Finally, periapical bone loss induced in wild-type mice were significantly diminished in MIF-/- mice. Altogether, the current study demonstrated that MIF appeared to function as a key costimulatory molecule to upregulate RANKL-mediated osteoclastogenesis, leading to the pathogenically augmented bone resorption in periradicular lesions. These data also suggest that the approach to neutralize MIF activity may lead to the development of a therapeutic regimen for the prevention of pathogenic bone loss in periradicular periodontitis.


Asunto(s)
Resorción Ósea/metabolismo , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Periodontitis Periapical/metabolismo , Animales , Resorción Ósea/inmunología , Modelos Animales de Enfermedad , Inflamación/inmunología , Inflamación/metabolismo , Factores Inhibidores de la Migración de Macrófagos/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Periodontitis Periapical/inmunología , Ligando RANK/inmunología , Ligando RANK/metabolismo
7.
Med Hypotheses ; 124: 87-90, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30798925

RESUMEN

Apical periodontitis represents a chronic inflammatory process within periapical tissues, mostly caused by etiological agents of endodontic origin. Progressive bone resorption in the periapical region represents the hallmark of apical periodontitis and occurs as the consequence of interplay between polymicrobial infections and host response. The Notch signaling pathway is an evolutionary conserved cell-signaling system that plays an important role in a variety of cell functions including proliferation, differentiation and apoptosis. In recent years its involvement in bone homeostasis has attracted a significant consideration. We hypothesized that Notch signaling pathway, which has a complex interplay with proinflammatory cytokines and bone resorption regulators, contributes to alveolar bone resorption via increased Notch receptors on immune cell surface and stimulates Notch receptor intracellular domain (NICD) translocation into the nucleus. The potential benefit of medications aimed to down-regulate these pathways in apical periodontitis treatment remains to be assessed.


Asunto(s)
Pérdida de Hueso Alveolar/metabolismo , Periodontitis Periapical/metabolismo , Receptores Notch/metabolismo , Transducción de Señal , Pérdida de Hueso Alveolar/fisiopatología , Animales , Huesos/metabolismo , Proliferación Celular , Citocinas/metabolismo , Humanos , Inflamación , Ligando RANK/metabolismo
8.
Clin Oral Investig ; 23(12): 4205-4212, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30806798

RESUMEN

To determine Toll-like receptors (TLR)2 and TLR4 expression levels and associate them with matrix metalloproteinases (MMPs) in asymptomatic apical periodontitis (AAP), symptomatic apical periodontitis (SAP), and healthy controls. Apical tissue/lesion samples were obtained from chronic AAP (n = 35) and SAP (n = 29), and healthy periodontal ligament (HPL, n = 10) with indication of tooth extraction, respectively. mRNA expression levels of TLR2, TLR4, MMP-1, MMP-2, MMP-8, and MMP-13 were determined by real-time reverse-transcription polymerase chain reaction. The data were analyzed with Kruskal-Wallis and Dunn's pot hoc test (p < 0.05). The correlation coefficient was obtained using the Spearman correlation (p < 0.05). TLR2, MMP-1, MMP-2, and MMP-13 mRNA levels were the highest in SAP followed by AAP and controls (p < 0.05). TLR4 and MMP-8 were over expressed in AAP and SAP compared to HPL (p < 0.05). TLR2 positively correlated with TLR4, MMP-1, MMP-8, and MMP-13 in SAP (p < 0.05). TLR2 and TLR4 are overexpressed in apical lesions versus healthy periodontal ligament and correlate with collagenolytic MMPs. Particularly, TLR2 is overexpressed in SAP in association with MMP-1, MMP-8, and MMP-13. Our results suggest that the activation of TLR2 along with MMP overexpression might contribute to SAP clinical presentation and progression. TLRs, MMPs, and their interaction can explain the clinical presentations and evolution of apical periodontitis and might represent key targets for new diagnostic and treatment approaches.


Asunto(s)
Metaloproteinasas de la Matriz/metabolismo , Periodontitis Periapical/metabolismo , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/metabolismo , Estudios Transversales , Humanos , Periodontitis Periapical/patología , Ligamento Periodontal/efectos de los fármacos , Ligamento Periodontal/metabolismo , Receptor Toll-Like 2/genética , Receptor Toll-Like 4/genética , Ápice del Diente/metabolismo
9.
Acta Odontol Scand ; 77(2): 142-149, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30394169

RESUMEN

OBJECTIVE: Endodontic originated chronic apical periodontitis (AP) is an inflammatory disease of periapical tissue. High-sensitivity C-reactive protein (hsCRP) as an inflammatory marker and hemogram indexes provide valuable information to clinicians for diagnosis, screening and follow-up of various diseases. The aim of this study was to investigate AP in terms of its association with hemogram indices and hsCRP levels. MATERIAL AND METHODS: Study includes 104 patients with AP and 40 participants as the control group. 160 teeth were diagnosed as AP through digital radiographic images and scored with respect to Periapical Index (PAI) scoring. Afterwards, patients were categorized into 3 grades in accordance with both the number and the severity of AP. AP grade 0 was considered for the control group with regard to a new scoring system. Patients with only one tooth involved with AP with a PAI score of 3 or 4 were categorized as an AP Grade 1, when a patient had more than one tooth with a PAI score of 3 or 4 he was classified as an AP Grade 2 and a patient with at least one tooth scored as a PAI 5 was rated as an AP Grade 3. Hemograms and hsCRP levels were measured for each individual to establish a correlation with inflammatory markers. RESULTS: The neutrophil/lymphocyte ratio (NLR) levels of patients with AP Grade 3 were significantly higher than all other AP grades (p < .05). hsCRP levels in patients with an AP Grade 2 and 3 were higher than both AP Grade 0 and 1 (p < .05). CONCLUSIONS: hsCRP levels of patients were reliable predictive indicators for AP severity in correlation with the new proposed scoring system for AP.


Asunto(s)
Proteína C-Reactiva/metabolismo , Linfocitos/metabolismo , Neutrófilos/metabolismo , Periodontitis Periapical/metabolismo , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodontitis Periapical/diagnóstico por imagen , Prevalencia , Radiografía Dental Digital , Diente no Vital/metabolismo , Adulto Joven
10.
Int Endod J ; 52(1): 5-12, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29904933

RESUMEN

AIM: To investigate the DNA methylation profiles of immune response-related genes in apical periodontitis (AP) lesions. METHODOLOGY: The methylation profiles on the cytosine-phosphate-guanine (CpG) regions of 22 gene promoters involved in inflammation and autoimmunity were assessed in 60 human AP lesions and 24 healthy periodontal ligaments (controls) using a pathway-specific real-time polymerase chain reaction array (EpiTect® Methyl Signature PCR Array Human Inflammatory Response). Differentially methylated genes were subsequently assessed for their mRNA expression. Data analyses (One-way anova, Tukey's multiple comparisons tests and Mann-Whitney tests) were performed using GraphPad Prism 6 software. P values ≤ 0.05 were considered statistically significant. RESULTS: Significant DNA hypermethylation was observed for CXCL3 and FADD gene promoters in AP lesions when compared to control tissues (P < 0.001) and among other genes (P < 0.05). In contrast, IL12B and IL4R were associated with significant hypomethylation in comparison to other genes (P < 0.05). IL12B, IL4R, CXCL3 and FADD had differential mRNA expression in AP lesions and controls (P < 0.001). CONCLUSIONS: Differential methylation profiles of immune response-related genes, such as FADD, CXCL3, IL12B and IL4R, may have an influence on individual AP susceptibility and patient treatment outcomes, through their potential contributions to altered expression of disease-relevant genes. Methylation and/or genetic variations in additional genes may also contribute to the dynamics of AP development and should be considered in future studies.


Asunto(s)
Metilación de ADN , Periodontitis Periapical/genética , Periodontitis Periapical/inmunología , Periodontitis Periapical/metabolismo , Transcriptoma , Adolescente , Adulto , Anciano , Autoinmunidad/genética , Brasil , Quimiocinas/genética , Quimiocinas CXC/genética , Citocinas/genética , Proteína de Dominio de Muerte Asociada a Fas/genética , Regulación de la Expresión Génica , Humanos , Inflamación , Subunidad p40 de la Interleucina-12/genética , Subunidad alfa del Receptor de Interleucina-4/genética , Persona de Mediana Edad , Ligamento Periodontal , Regiones Promotoras Genéticas , ARN Mensajero/biosíntesis , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores de Citocinas/genética , Adulto Joven
11.
Acta Odontol Scand ; 77(3): 173-180, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30585523

RESUMEN

Apical periodontitis caused by root canal infection is the most frequent pathological lesion in the jaws, mainly manifested as periapical granulomas and cysts. Understanding of the formation and progression of apical periodontitis as well as the identification of inflammatory biomarkers can help increase the knowledge of pathogenic mechanisms, improve the diagnosis and provide support for different therapeutic strategies. The objective of the present article is to review inflammatory biomarkers such as cytokines, chemokines, inflammatory cells, neuropeptides, RANK/RANKL/OPG system and other inflammatory markers and to relate these systems to the development and progression of pathological conditions related to apical periodontitis.


Asunto(s)
Inflamación/metabolismo , Osteoprotegerina/metabolismo , Periodontitis Periapical/metabolismo , Tratamiento del Conducto Radicular/efectos adversos , Biomarcadores , Humanos
12.
Cell Physiol Biochem ; 49(3): 884-898, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30184545

RESUMEN

BACKGROUND/AIMS: Periapical periodontitis is caused by bacterial infection and results in both one destruction and tooth loss. Osteopontin (OPN) is a secreted phosphorylated glycoprotein that participates in bone metabolism. METHODS: Thirty-three patients with chronic periapical periodontitis and 10 patients who had undergone the orthodontic removal of healthy tooth tissue (control) at the periodontal ligament were investigated, and an animal model of mouse periapical periodontitis was established for an in vivo analysis. The relationship between OPN and bone destruction during periapical periodontitis was analyzed. Osteoblasts and osteoclasts were cultured in vitro and treated with lipopolysaccharide. An inhibitor of NF-κB was used to pretreat the transfected cells. RESULTS: OPN increased osteoclast proliferation and differentiation, but reduced osteoblasts proliferation and differentiation. OPN activated the NF-κB pathway during periapical periodontitis and accelerated the transfer and phosphorylation of P65 from the cytoplasm to the nucleus. CONCLUSION: This study demonstrated that OPN played important roles in the progression of periapical periodontitis, and a dual role in bone metabolism during periapical periodontitis, linking osteoclasts and osteoblasts. The underlying mechanism may be related to the NF-κB pathway.


Asunto(s)
FN-kappa B/metabolismo , Osteopontina/metabolismo , Periodontitis Periapical/patología , Transducción de Señal , Animales , Catepsina K/genética , Catepsina K/metabolismo , Diferenciación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Masculino , Mandíbula/diagnóstico por imagen , Ratones , Ratones Endogámicos C57BL , Osteopontina/antagonistas & inhibidores , Osteopontina/genética , Periodontitis Periapical/diagnóstico por imagen , Periodontitis Periapical/metabolismo , Tejido Periapical/diagnóstico por imagen , Tejido Periapical/metabolismo , Ligamento Periodontal/metabolismo , Células RAW 264.7 , Interferencia de ARN , ARN Interferente Pequeño/metabolismo
13.
J Appl Oral Sci ; 26: e20170512, 2018 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-29995146

RESUMEN

OBJECTIVE: To evaluate and correlate, in the same research, the mRNA expression and the staining of RANK, RANKL, OPG, TLR2 and MyD88 by immunohistochemistry in the apical periodontitis (AP) progression in mice. MATERIAL AND METHODS: AP was induced in the lower first molars of thirty-five C57BL/6 mice. They were assigned to four groups according to their euthanasia periods (G0, G7, G21 and G42). The jaws were removed and subjected to histotechnical processing, immunohistochemistry and real-time reverse transcription-PCR (qRT-PCR). Data were analyzed with parametric and nonparametric tests (α=0.05). RESULTS: An increase of positive immunoreactivity for RANK, RANKL, OPG, TLR2 and MyD88 was observed over time (p<0.05). The RANKL expression was different between the groups G0 and G42, G21 and G42 (p=0.006), with G42 presenting the higher expression in both comparations. The OPG expression was statistically different between the groups G0 and G7, G7 and G21 and G7 and G42 (p<0.001), with G7 presenting higher expression in all the time points. The TLR2 expression was different between the groups G0 and G42 (p=0.03), with G42 showing the higher expression. The MyD88 expression presented a statistical significant difference between groups G7, G21 and G42 compared with G0 (p=0.01), with G0 presenting the smallest expression in all the comparisons. The Tnfrsf11/Tnfrsf11b (RANKL/OPG) ratio increased with the AP progression (p=0.002). A moderate positive correlation between MyD88 and RANKL (r=0.42; p=0.03) and between MyD88 and TLR2 (r=0.48; p<0.0001) was observed. CONCLUSION: The expression of the RANK, RANKL, OPG, MyD88 and TLR2 proteins as well as the ratio Tnfrsf11/Tnfrsf11b (RANKL/OPG) increased with AP progression. There was also a moderate positive correlation between the expression Myd88-Tnfrsf11 and Tlr2-Myd88, suggesting the relevance of Tlr2-Myd88 in bone loss due to bacterial infection.


Asunto(s)
Factor 88 de Diferenciación Mieloide/análisis , Osteoprotegerina/análisis , Periodontitis Periapical/metabolismo , Ligando RANK/análisis , ARN Mensajero/análisis , Receptor Toll-Like 2/análisis , Animales , Progresión de la Enfermedad , Expresión Génica , Inmunohistoquímica , Masculino , Ratones Endogámicos C57BL , Periodontitis Periapical/patología , Valores de Referencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo
14.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 53(1): 20-25, 2018 Jan 09.
Artículo en Chino | MEDLINE | ID: mdl-29972959

RESUMEN

Objective: To investigate the distribution of fimA and kgp genotypes as well as the common genotype combination of Porphyromonas gingivalis (Pg) in infected root canals of primary apical periodontitis for virulent isolates screening in future. Methods: Thirty-four samples harboring Pg were selected from infected root canals of primary apical periodontitis from patients of the Department of Endodontics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from June 2013 to September 2015. FimA type-specific primers were used to amplify the samples, revealing the distribution of various fimA genotypes. The genotypes of kgp were obtained by using Mse Ⅰ restriction endonuclease. The prevalence of each genotype and common genotype combinations were then calculated. Pearson's chi-squared test was performed to analyze the correlation between genotype combinations and clinical symptoms and major signs of apical periodontitis. In addition, the bioflim architectures between Pg isolates with different fimA and kgp genotype combinations were observed compared using confocal laser scanning microscope. Results: Among the 34 Pg-positive samples, fimA Ⅱ was the most prevalent genotype [47% (16/34)] followed by fimA Ⅰ [26% (9/34)], while fimA Ⅴ was detected in only one sample. The prevalence of kgp Ⅰ [56% (19/34)] was slightly higher than that of kgp Ⅱ [44% (15/34)]. Both fimA Ⅱ+kgp Ⅰ and fimAⅡ+kgp Ⅱ were the most prevalent genotype combinations [24% (8/34) each]. No significant correlation was found between specific genotype combination and such major clinical manifestations as gingival swelling and sinus tract of dental origin (P>0.05). Three Pg isolates with different genotype combinations were acquired. Isolate A (fimAⅠ+kgpⅠ) formed densest biofilm, while the biofilm of isolate C (fimAⅤ+kgp Ⅰ) was much looser. The biofilm feature of isolate B (fimAⅢ+kgp Ⅱ) fell in between A and C. Conclusions: Pg with fimA Ⅱ was most frequently detected in infected root canals of primary apical periodontitis. The prevalence of Pg with kgp Ⅰ was slightly higher than that with kgp Ⅱ, and fimAⅡ+kgp Ⅰ as well as fimA Ⅱ+kgp Ⅱ were the commonest genotype combinations. According to the comparison of Pg biofilms formed by clinical isolates, it might be possible that different genotype combinations may lead to distinct biofilm architectures.


Asunto(s)
Adhesinas Bacterianas/genética , Cisteína Endopeptidasas/genética , Cavidad Pulpar/microbiología , Proteínas Fimbrias/genética , Genotipo , Periodontitis Periapical/microbiología , Porphyromonas gingivalis/genética , Adhesinas Bacterianas/metabolismo , China , Cisteína Endopeptidasas/metabolismo , Cartilla de ADN , Proteínas Fimbrias/metabolismo , Humanos , Periodontitis Periapical/metabolismo , Reacción en Cadena de la Polimerasa , Porphyromonas gingivalis/metabolismo
15.
Int J Oral Sci ; 10(2): 12, 2018 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-29654284

RESUMEN

Hypoxia (low oxygen level) is an important feature during infections and affects the host defence mechanisms. The host has evolved specific responses to address hypoxia, which are strongly dependent on the activation of hypoxia-inducible factor 1 (HIF-1). Hypoxia interferes degradation of HIF-1 alpha subunit (HIF-1α), leading to stabilisation of HIF-1α, heterodimerization with HIF-1 beta subunit (HIF-1ß) and subsequent activation of HIF-1 pathway. Apical periodontitis (periapical lesion) is a consequence of endodontic infection and ultimately results in destruction of tooth-supporting tissue, including alveolar bone. Thus far, the role of HIF-1 in periapical lesions has not been systematically examined. In the present study, we determined the role of HIF-1 in a well-characterised mouse periapical lesion model using two HIF-1α-activating strategies, dimethyloxalylglycine (DMOG) and adenovirus-induced constitutively active HIF-1α (CA-HIF1A). Both DMOG and CA-HIF1A attenuated periapical inflammation and tissue destruction. The attenuation in vivo was associated with downregulation of nuclear factor-κappa B (NF-κB) and osteoclastic gene expressions. These two agents also suppressed NF-κB activation and subsequent production of proinflammatory cytokines by macrophages. Furthermore, activation of HIF-1α by DMOG specifically suppressed lipopolysaccharide-stimulated macrophage differentiation into M1 cells, increasing the ratio of M2 macrophages against M1 cells. Taken together, our data indicated that activation of HIF-1 plays a protective role in the development of apical periodontitis via downregulation of NF-κB, proinflammatory cytokines, M1 macrophages and osteoclastogenesis.


Asunto(s)
Pérdida de Hueso Alveolar/metabolismo , Pérdida de Hueso Alveolar/prevención & control , Subunidad alfa del Factor 1 Inducible por Hipoxia/fisiología , Periodontitis Periapical/metabolismo , Periodontitis Periapical/prevención & control , Aminoácidos Dicarboxílicos/farmacología , Animales , Citocinas/metabolismo , Regulación hacia Abajo , Expresión Génica/efectos de los fármacos , Macrófagos/fisiología , Ratones , FN-kappa B/metabolismo , Osteogénesis/fisiología , Reacción en Cadena en Tiempo Real de la Polimerasa , Microtomografía por Rayos X
16.
J Endod ; 44(5): 780-785, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29550006

RESUMEN

INTRODUCTION: The aim of this study was to evaluate the gene expression of proinflammatory cytokines, matrix metalloproteinases (MMPs), and cathepsin K in apical periodontitis (AP) and the volume of lesions in ovariectomized and sham-operated rats. METHODS: Twenty 12-week-old female Wistar rats were subjected to ovariectomy (OVX) or sham surgery. After 9 weeks, access cavities were prepared in the maxillary and mandibular first molars, pulp tissue was removed, and canals were exposed to the oral environment during 21 days for the induction of AP. The groups were as follows: sham, OVX, sham+AP, and OVX+AP. Animals were euthanized, and blocks containing the maxillary first molar and the surrounding bone were removed for quantification of proinflammatory cytokines cathepsin K and MMP genes by real-time polymerase chain reaction. The hemimandibles containing the mandibular first molars were used for analysis of the AP lesion volume by micro-computed tomographic imaging. RESULTS: AP in OVX rats showed an increased expression of interleukin 1 beta, tumor necrosis factor alpha, interleukin 6, MMP-8, and MMP-13 (P < .05). OVX alone, without AP induction, did not affect the expression of the evaluated genes. Additionally, AP induced an increase in cathepsin K expression, without significant differences between AP in the sham and OVX groups (P > .05). Micro-computed tomographic imaging showed a significantly greater AP lesion mean volume in OVX compared with sham animals (P < .05). CONCLUSIONS: AP lesions in ovariectomized rats are larger and have an increased expression of proinflammatory cytokines and MMPs, indicating that the infection combined with ovariectomy has an important role in the regulation of these signaling molecules and enzymes during the development of AP. Based on that, it may be assumed that the hypoestrogenic condition aggravates inflammation and degradation of extracellular matrix components in AP, which may provide insight into understanding the development of AP in female postmenopausal patients.


Asunto(s)
Citocinas/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Ovariectomía/efectos adversos , Periodontitis Periapical/etiología , Animales , Catepsina K/metabolismo , Femenino , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 8 de la Matriz/metabolismo , Periodontitis Periapical/metabolismo , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor de Necrosis Tumoral alfa/metabolismo
17.
Oral Dis ; 24(1-2): 57-62, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29480630

RESUMEN

INTRODUCTION: Clastic cells, originating from the monocyte-macrophage lineage, resorb mineralized tissues. In periapical periodontitis, alveolar bone around the tooth apex becomes resorbed; however, the roots of the teeth are often left intact by yet unknown mechanisms. Here, we examined the status of clastic cells in a periapical periodontitis model in mice. METHODS: Periapical periodontitis was induced by performing pulp exposure on the maxillary first molar. The contralateral maxillary first molar was used as a control. The maxillae were harvested, fixed, and subjected to µCT scanning and three-dimensional volumetric analysis. TRAP staining was performed, and osteoclasts were quantified. Immunohistochemical staining was performed for RANKL, OPG, and F4/80, a marker for macrophages. RESULTS: At the apex of the tooth, pulp exposure resulted in periapical radiolucency with mineralized tissues at the surrounding bone surfaces but not on the root surfaces. Histologically, clastic cells were present on the bone surfaces but absent around the root surfaces. Expression of F4/80 and RANKL was not found at close proximity to the root surfaces, but OPG was globally expressed. CONCLUSION: The absence of clastic cells around the root surface of pulp-exposed teeth, in part, is associated with the lack of macrophages and RANKL expression.


Asunto(s)
Proceso Alveolar/diagnóstico por imagen , Maxilar/diagnóstico por imagen , Osteoclastos/patología , Periodontitis Periapical/diagnóstico por imagen , Raíz del Diente/diagnóstico por imagen , Proceso Alveolar/metabolismo , Proceso Alveolar/patología , Animales , Antígenos de Diferenciación/metabolismo , Pulpa Dental , Modelos Animales de Enfermedad , Femenino , Macrófagos/patología , Maxilar/metabolismo , Maxilar/patología , Ratones , Diente Molar , Osteoprotegerina/metabolismo , Periodontitis Periapical/metabolismo , Periodontitis Periapical/patología , Ligando RANK/metabolismo , Raíz del Diente/metabolismo , Raíz del Diente/patología , Microtomografía por Rayos X
18.
Braz. dent. j ; 29(1): 43-47, Jan.-Feb. 2018. tab, graf
Artículo en Inglés | LILACS | ID: biblio-888722

RESUMEN

Abstract The aim of this study was to evaluate the expression of MMP2 and MMP9 during apical periodontitis (AP) progression in TLR2 (TLR2 KO) and in MyD88 (MyD88 KO) knockout mice compared to wild type (WT) mice. AP was induced in mandibular first molars of TLR2 KO (n= 18), MyD88 KO (n= 18), and WT mice (n= 18). After 7, 21, and 42 days, the animals were euthanized and the jaws were dissected and subjected to histotechnical processing. Subsequent sections were stained by immunohistochemistry and evaluated for detection of MMP2 and MMP9. Statistical analysis of the semi-quantitative analysis of immunohistochemistry was performed using chi-square test (α = 0.05). In the initial periods of AP progression, an increased expression of MMP9 in the TLR2 KO and MyD88 KO mice was observed. In the final periods of AP progression, a reduction of MMP2 expression and an increase of MMP9 expression in the TLR2 KO mice were observed. MMP2 and MMP9 production was modulated for TLR2 and MyD88 during apical periodontitis progression.


Resumo O objetivo deste estudo foi avaliar a expressão de MMP2 e MMP9 durante a progressão da periodontite apical (AP) em camundongos knockout para TLR2 (TLR2 KO) e MyD88 (MyD88 KO) comparados aos camundongos wild type (WT). A AP foi induzida nos primeiros molares inferiores dos camundongos TLR2 KO (n = 18), MyD88 KO (n = 18) e WT (n = 18). Após 7, 21 e 42 dias, os animais foram eutanaziados e as mandíbulas foram dissecadas e submetidas a processamento histotécnico. As lâminas foram coradas por imuno-histoquímica e analisadas para a detecção de MMP2 e MMP9. A análise estatística semi-quantitativa da imuno-histoquímica foi realizada pelo teste qui-quadrado (α = 0,05). Nos períodos iniciais de progressão AP, foi observada uma expressão aumentada de MMP9 nos camundongos TLR2 KO e MyD88 KO. Nos períodos finais de progressão AP, observou-se uma redução da expressão de MMP2 e um aumento da expressão de MMP9 nos camundongos TLR2 KO. A produção de MMP2 e MMP9 foi modulada por TLR2 e MyD88 durante a progressão da periodontite apical.


Asunto(s)
Animales , Ratones , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Factor 88 de Diferenciación Mieloide/fisiología , Periodontitis Periapical/enzimología , Receptor Toll-Like 2/fisiología , Progresión de la Enfermedad , Inmunohistoquímica , Ratones Endogámicos C57BL , Ratones Noqueados , Factor 88 de Diferenciación Mieloide/genética , Periodontitis Periapical/metabolismo , Periodontitis Periapical/patología
19.
Int Endod J ; 51(7): 747-757, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29363137

RESUMEN

AIM: To investigate the role played by silent information regulator 2 homologue 1 (SIRT1) during angiogenesis of periapical periodontitis. METHODOLOGY: Periapical granulomas were subjected to dual-colour immunofluorescence imaging and real-time polymerase chain reactions assaying the expression levels of SIRT1, vascular endothelial growth factor (VEGF) and VE-cadherin. The association between Ki-67 and SIRT1 expression was also examined. Human umbilical vein endothelial cells (HUVECs) were treated with a combination of lipopolysaccharide and resveratrol (a SIRT1 activator) or sirtinol (a SIRT1 inhibitor); and the levels of mRNAs encoding SIRT1, VEGF and VE-cadherin were determined. HUVEC tube formation was assayed in the presence of resveratrol or sirtinol. The Mann-Whitney U-test or the Tukey-Kramer test was used for statistical analysis. RESULTS: Ki-67-expressing cells, including endothelial cells, lay adjacent to SIRT1-expressing cells in periapical granulomas. In addition, SIRT1-expressing cells were detected adjacent to VEGF-expressing cells and VEGF- or VE-cadherin-expressing endothelial cells. SIRT1, VEGF and VE-cadherin mRNA expression levels in periapical granulomas were significantly higher (P = 0.0054, 0.0090 and 0.0090, respectively) than those in healthy gingival tissues. HUVECs treated with resveratrol exhibited significantly higher expression of mRNAs encoding SIRT1, VEGF and VE-cadherin (P = 0.0019, 0.00005 and 0.0045, respectively) compared with controls, but sirtinol inhibited such expression. Resveratrol caused HUVECs to form tube-like structures, whilst sirtinol inhibited this process. CONCLUSIONS: These findings suggest that SIRT1 may stimulate angiogenesis in periapical granulomas by triggering the proliferation of endothelial cells and inducing VEGF and VE-cadherin expression.


Asunto(s)
Periodontitis Periapical/metabolismo , Sirtuina 1/metabolismo , Adulto , Anciano , Antígenos CD/metabolismo , Cadherinas/metabolismo , Proliferación Celular , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Neovascularización Patológica/metabolismo , Granuloma Periapical/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Resveratrol/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto Joven
20.
Int Endod J ; 51(7): 738-746, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29363148

RESUMEN

AIM: To evaluate the association between the presence of selected bacterial species/groups in the apical root canal and expression of mediators of soft and bone tissue destruction in apical periodontitis lesions. Relationships between bacteria and some other features of apical periodontitis were also investigated. METHODOLOGY: Seventeen freshly extracted teeth with pulp necrosis and apical periodontitis were included. The apical root segment was sectioned and cryopulverized; DNA was extracted and evaluated for the presence of 9 bacterial species/groups using real-time polymerase chain reaction. Lesions were processed for histopathological and immunohistochemical analyses, which targeted matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9), receptor activator of NFκB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG). Associations of the target bacteria with expression of these mediators, presence of symptoms, lesion size and histopathological diagnosis were evaluated. Data were analysed using the chi-square, Fisher's exact, Mann-Whitney and Pearson tests. P values lower than 0.05 were considered significant. RESULTS: All pulverized apical root samples were positive for bacteria. The most prevalent taxa were Actinobacteria (53%), Streptococcus species (35%), Fusobacterium species and Parvimonas micra (18%). The target mediators exhibited a high mean expression in the lesions (MMP-2: 82%; MMP-9: 73%; RANK: 78%; RANKL; 81%; OPG; 83%). Mean RANKL:OPG ratio was significantly higher in granulomas than cysts (P < 0.05, Mann-Whitney test). Actinobacteria were associated with granulomas, higher MMP-2 expression, lower OPG expression, and higher RANKL:OPG ratio (P < 0.05 for all, Fisher's exact test or Mann-Whitney test). No other significant associations were found. CONCLUSION: Actinobacteria may play an important role in the active phase of soft and bone tissue destruction in apical periodontitis.


Asunto(s)
Cavidad Pulpar/microbiología , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Osteoprotegerina/metabolismo , Periodontitis Periapical/microbiología , Ligando RANK/metabolismo , Receptor Activador del Factor Nuclear kappa-B/metabolismo , Ápice del Diente/microbiología , Adulto , Anciano , Cavidad Pulpar/metabolismo , Necrosis de la Pulpa Dental/metabolismo , Necrosis de la Pulpa Dental/microbiología , Femenino , Fusobacterium , Humanos , Masculino , Persona de Mediana Edad , Periodontitis Periapical/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Streptococcus , Ápice del Diente/metabolismo
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