Development Of Apical Periodontitis Research Articles

27-Hydroxycholesterol contributes to hypercholesterolemia-associated aggravation of apical periodontitis in ovariectomized rats and raloxifene counteracts its action.

The influence of hypercholesterolemia on the development of apical periodontitis (AP) is inconclusive. Recent studies revealed that cholesterol metabolite 27-hydoxycholesterol (27HC) can affect cellular responses to bacterial infections and oestrogen status and raloxifene may influence its action. Herein, we aimed to examine the impact of 27HC on production of inflammatory mediators by macrophages and the regulatory function of raloxifene. The contribution of 27HC to AP development and the therapeutic effect of raloxifene were evaluated in a rat model. Murine macrophages J774 cells were used. The expression of inducible nitric oxide synthase (iNOS) was examined by Western blot. The concentrations of C-C motif chemokine ligand (CCL) 2 and 27HC were assessed by enzyme-linked immunosorbent assay. Colorimetric assay was used to evaluate cholesterol levels. Experimental AP was induced in ovariectomized (OVX) or un-operated rats receiving high-fat/high-cholesterol diet (HFHCD) or normal diet (ND). Micro-computed tomography and immunohistochemistry were employed to evaluate disease severity and the therapeutic effect of raloxifene. Cholesterol enhanced 27HC production in macrophages. 27HC induced iNOS and CCL2 synthesis by macrophages and estradiol suppressed the responses. In our animal model of AP, HFHCD plus OVX significantly augmented serum and lesion tissue levels of 27HC (p < .05 versus the ND group). Lesion size, infiltration of CD68+ cells, and iNOS+ monocytes were increased in parallel with 27HC accumulation. Raloxifene inhibited pro-inflammatory effects of 27HC on macrophages and suppressed AP progression in HFHCD/OVX rats (p < .05 versus the vehicle control group). Our results suggested that 27HC contributes to AP aggravation associated with hypercholesterolemia. Oestrogen deficiency may both enhance 27HC production and exacerbate its downstream action.

Osteoporosis and Apical Periodontitis Prevalence: A Systematic Review.

Osteoporosis is a common systemic bone disorder in the elderly, characterized by low bone mineral density and deterioration of bone structure. Apical periodontitis is an inflammatory response to the microbial infection of root canals, typically characterized by apical bone destruction surrounding the tooth's apex. This systematic review aimed to determine if osteoporosis affects the prevalence of apical periodontitis in adults. PRISMA guidelines have been followed. It included randomized clinical trials, cross-sectional, cohort, and case-control studies, and excluded non-relevant investigations and various secondary sources. A comprehensive search was performed in PubMed, Scopus, and Web of Science, until 13 March 2024. The Newcastle-Ottawa Scale was used to assess the quality of the three selected studies: two cross-sectional studies and one case-control study. One investigation only included post-menopausal women recruited at a dental university clinic, the other integrated data from the total hospital patients' population, and the third selected patients referred to the university dental clinic from the university hospital. The findings varied: one study noted a marginal association between low bone mineral density and apical periodontitis, another found a significant association, and the third, with the lowest risk of bias, reported no link. The main limitations were the scarcity of eligible studies and their overall quality. The review was registered in the PROSPERO database (CRD42024523705), applied strict inclusion criteria and thorough searches by experienced and independent reviewers. There is no strong evidence that adult individuals with osteoporosis have a higher probability of developing apical periodontitis. However, clinicians should remain cautious of osteoporosis's potential impact on apical periodontitis development.

Assessment of the Need for Surgical Debridement of Periapical Tissues Among Patients of Older Age Groups as a Manifestation of Ageism

Endodontic therapy is aimed at cleaning the root canal system and creating barriers to prevent re-infection of roots and peripical tissues. The presence of persistent bacteria or reinfection of a previously mechanically treated and disinfected root system causes the development of apical periodontitis and the need to implement surgical aids. Against the background of an increase in the number of patients of older age groups, characterized by obliteration of the root canal system, the relevance of surgical aids for apical periodontitis increases. At the same time, based on their own life experience, patients of older age groups may perceive the refusal to perform orthodontic therapy and the offer of surgical benefits as age-related egoism. Purpose of work: to study the severity of periapical changes and indications for surgical intervention among patients of older age groups. Materials and methods. The endodontic and periapical status of 300 patients was assessed in the 1st subgroup aged 60 to 70 years and the 2nd subgroup aged over 71 years. The results of the study. The greatest number of ageist conclusions in assessing the feasibility of providing surgical benefits was revealed in women with higher education.

Milk-derived small extracellular vesicles inhibit the MAPK signaling pathway through CD36 in chronic apical periodontitis

BackgroundSmall 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. ResultsThe 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. ConclusionsCD36 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.

Enterococcus faecalis Extracellular Vesicles Promote Apical Periodontitis

Enterococcus faecalis is an important contributor to the persistence of chronic apical periodontitis. However, the mechanism by which E. faecalis infection in the root canals and dentinal tubules affects periapical tissue remains unclear. Bacterial extracellular vesicles (EVs) act as natural carriers of microbe-associated molecular patterns (MAMPs) and have recently attracted considerable attention. In this study, we investigated the role of EVs derived from E. faecalis in the pathogenesis of apical periodontitis. We observed that E. faecalis EVs can induce inflammatory bone destruction in the periapical areas of mice. Double-labeling immunofluorescence indicated that M1 macrophage infiltration was increased by E. faecalis EVs in apical lesions. Moreover, in vitro experiments demonstrated the internalization of E. faecalis EVs into macrophages. Macrophages tended to polarize toward the M1 profile after treatment with E. faecalis EVs. Pattern recognition receptors (PRRs) can recognize MAMPs of bacterial EVs and, in turn, trigger inflammatory responses. Thus, we performed further mechanistic exploration, which showed that E. faecalis EVs considerably increased the expression of NOD2, a cytoplasmic PRR, and that inhibition of NOD2 markedly reduced macrophage M1 polarization induced by E. faecalis EVs. RIPK2 ubiquitination is a major downstream of NOD2. We also observed increased RIPK2 ubiquitination in macrophages treated with E. faecalis EVs, and E. faecalis EV-induced macrophage M1 polarization was notably alleviated by the RIPK2 ubiquitination inhibitor. Our study revealed the potential for EVs to be considered a virulence factor of E. faecalis and found that E. faecalis EVs can promote macrophage M1 polarization via NOD2/RIPK2 signaling. To our knowledge, this is the first report to investigate apical periodontitis development from the perspective of bacterial vesicles and demonstrate the role and mechanism of E. faecalis EVs in macrophage polarization. This study expands our understanding of the pathogenic mechanism of E. faecalis and provides novel insights into the pathogenesis of apical periodontitis.

The use of modern technologies and the machine system Reciproc (VDW) during the revision of the root canals of a tooth with apical periodontitis: a case report

Endodontic retreatment in most cases is indicated with the development of apical periodontitis in teeth with previously treated root canals. This treatment is complicated by the fact that the root canals can be lined with any material: guttapercha pins, paste, cement, anchor and fiberglass pins, resorcinol-formalin paste, fragments of tools can be located in the channels at any level and root canal transportation can occur. The choice of endodontic treatment or tooth extraction is always before dentists. The availability of modern machine files, ultrasound attachments, filling materials and X–ray examinations in the assortment of doctors makes it much easier for dentists and therapists to conduct endodontic treatment and improves its quality. This article presents a clinical case of repeated endodontic treatment of a 2.6 tooth with apical periodontitis and a clinical picture of chronic sinusitis. The article shows the main stages of treatment, the results of X-ray examinations, microbiological examination of the root canal biofilm before and after mechanical treatment with the Reciproc endosystem and long-term results, which will help practicing dentists during root canal revision.

RvE1 Promotes Axin2+ Cell Regeneration and Reduces Bacterial Invasion

Vital pulp therapy and root canal therapy (RCT) are the dominant treatment for irreversible pulpitis. While the success rate of these procedures is favorable, they have some limitations. For instance, RCT leads to removing significant dentin in the coronal third of the tooth that increases root-fracture risk, which forces tooth removal. The ideal therapeutic goal is dental pulp regeneration, which is not achievable with RCT. Specialized proresolving mediators (SPMs) are well known for inflammatory resolution. The resolution of inflammation and tissue restoration or regeneration is a dynamic and continuous process. SPMs not only have potent immune-modulating functions but also effectively promote tissue homeostasis and regeneration. Resolvins have been shown to promote dental pulp regeneration. The purpose of this study was to explore further the cellular target of Resolvin E1 (RvE1) therapy in dental pulp regeneration and the impact of RvE1 in infected pulps. We investigated the actions of RvE1 on experimentally exposed pulps with or without microbial infection in an Axin2 Cre-Dox ;Ai14 genetically defined mouse model. Our results showed RvE1 promoted Axin2-tdTomato+ cell expansion and odontoblastic differentiation after direct pulp capping in the mouse, which we used to mimic reversible pulpitis cases in the clinic. In cultured mouse dental pulp stem cells (mDPSCs), RvE1 facilitated Axin2-tdTomato+ cell proliferation and odontoblastic differentiation and also rescued impaired functions after lipopolysaccharide stimulation. In infected pulps exposed to the oral environment for 24 h, RvE1 suppressed inflammatory infiltration, reduced bacterial invasion in root canals, and prevented the development of apical periodontitis, while its proregenerative impact was limited. Collectively, topical treatment with RvE1 facilitated dental pulp regenerative properties by promoting Axin2-expressing cell proliferation and differentiation. It also modulated the resolution of inflammation, reduced infection severity, and prevented apical periodontitis, presenting RvE1 as a novel therapeutic for treating endodontic diseases.

A novel analysis of the formation and resorption changes in dental hard tissue using longitudinal in vivo micro computed tomography.

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.

SMAD2/3 Phosphorylation is correlated with matrix metalloproteinase 9 expression in human periapical lesions

ObjectiveThe aim of this study was to investigate the presence of phosphorylated SMAD2/3 (P-SMAD2/3) in periapical lesions in humans and its possible correlation with matrix metalloproteinase 9 (MMP9) during the development of apical periodontitis. DesignIn this study, a total of 38 samples were collected, consisting of 16 healthy controls and 22 periapical lesions. These samples underwent fixation, dehydration, and embedding for further histologic and immunochemical analysis. The expression of phosphorylated SMAD2/3 and MMP9 was quantified using the average integrated optical density. Additionally, immunofluorescence analysis was conducted to investigate the colocalization of phosphorylated SMAD2/3 and MMP9. ResultsThe study found that periapical lesions exhibited a stronger expression of MMP9 compared to healthy controls. Additionally, the expression of phosphorylated SMAD2/3 was observed to increase in the periapical granulomas and radicular cysts group, as compared to the normal group (P < 0.01). The results of the immunofluorescence test showed that phosphorylated SMAD2/3 was colocalized with MMP9. ConclusionsThe study found that SMAD2/3 phosphorylation is correlated with matrix metalloproteinase 9 expression in human periapical lesions, suggesting its potential involvement in tissue destruction and immune cell infiltration in periapical lesions.

Reparative Dentin Formation Following Dental Pulp Capping is Mediated by TNFR1 In Vivo

IntroductionTumor necrosis factor (TNF)-α is a pro-inflammatory cytokine that promotes biomineralization in vitro in dental pulp cells. However, the role of TNF-α-TNF receptor 1 (TNFR1) signaling in reparative dentin formation and related inflammatory pathways is not known. Therefore, the aim of this study was to evaluate the role of the TNF-α-TNFR1 axis in dental pulp repair following pulp capping in vivo. MethodsDental pulp repair response of genetically deficient TNF-α receptor-1 mice (TNFR1−/−; n = 20) was compared with that of C57Bl6 mice (wild type [WT]; n = 20). Pulp capping was performed with mineral trioxide aggregate on the mandibular first molars of mice. After 7 and 70 days, tissues were collected and stained with hematoxylin and eosin for histopathological and histometric evaluation, and assessed by the Brown and Brenn methods for histomicrobiological analysis and by immunohistochemistry to localize TNF-α, Runt-related transcription factor 2, Dentin Sialoprotein (DSP) and Osteopontin (OPN) expression. ResultsCompared with WT mice, TNFR1−/− mice showed significantly decreased reparative dentin formation with a lower mineralized tissue area (P < .0001). Unlike WT mice, TNFR1−/− mice also exhibited significant dental pulp necrosis, neutrophil recruitment, and apical periodontitis formation (P < .0001) without bacterial tissue invasion. TNFR1−/− animals further exhibited decreased TNF-α, DSP, and OPN expression (P < .0001), whereas Runt-related transcription factor 2 expression was unchanged (P > .05). ConclusionThe TNF-α-TNFR1 axis is involved in reparative dentin formation following dental pulp capping in vivo. Genetic ablation of TNFR1 modified the inflammatory process and inhibited the expression of the DSP and OPN mineralization proteins, which culminated in dental pulp necrosis and development of apical periodontitis.

Comparative analysis of the effectiveness of modern irrigants activation techniques in the process of mechanical root canal system treatment (Literature review)

Development of apical periodontitis is the most common complication of unsuccessful endodontic treatment. Cleaning the root canal system is a crucial stage and the main factor for a successful endodontic protocol. Inability to remove debris from inaccessible branches of the root canal system, especially from the apical region, leads to and increases the risk of secondary infection. Selection of the optimal method for activating irrigants remains a current issue. According to the results of several studies, none of the individual irrigation activation techniques allows achieving ideal cleanliness in the root canal, but the use of laser, sonic, multisonic, and ultrasonic activation significantly improves the quality of cleaning and provides a prolonged antimicrobial effect by enhancing the diffusion of intracanal antiseptics, their hydrolytic and antibacterial effectiveness, which will eventually ensure maximum adhesion of filling materials. This, in turn, indicates the absence of a unified protocol that would provide stable irrigation efficiency and long-term results in endodontic treatment. The use of a protocol with combined activation of irrigants remains an open question among clinicians and scientists.

RGS10 Negatively Regulates Apical Periodontitis via TFEB-mediated Autophagy in BABL/c Mice Model and in vitro.

Apical periodontitis is a prevalent oral inflammatory disease that has recently been linked to transcription factor EB (TFEB)-mediated autophagy. Regulator of G-protein signaling 10 (RGS10) is reported to be an effective regulator of the immune system and inflammation. This study aimed to investigate the involvement of RGS10 during the development of apical periodontitis through the TFEB-mediated autophagy signaling pathway. Sixty BALB/c mice were randomly divided into four groups of fifteen mice for the in vivo experiment. Rgs10 was locally overexpressed through eight injections of an adeno-associated virus vector. The model of apical periodontitis was established 21 days following pulp exposure, and the mice were euthanized to obtain mandibles for analysis. Micro-computed tomography was employed to assess alveolar bone destruction, and the levels of Rgs10, TFEB-mediated autophagy signaling factors, and inflammatory factors were measured using quantitative reverse transcription polymerase chain reactions, western blotting, enzyme-linked immunosorbent assays, immunofluorescence, and immunohistochemistry. All experimental results were displayed as images or graphs. For the in vitro experiments, we employed small interfering RNA (siRNA) to silence Rgs10 expression in RAW 264.7 cells. The data were analyzed via one-way ANOVA or Mann-Whitney U test/ Kruskal-Wallis test of variance, where P < 0.05 or U > 1.96 was considered statistically significant. Local overexpression of Rgs10 reduced alveolar bone destruction within the apical periodontitis lesion and significantly decreased macrophage infiltration (P < 0.05). Meanwhile, the expression of TFEB-mediated autophagy signaling factors was upregulated, along with a decrease in inflammatory factor expression (P < 0.05). Lipopolysaccharide-stimulated RAW 264.7 cells exhibited decreased Rgs10 expression and TFEB-mediated autophagy signaling. siRNA-mediated silencing of Rgs10 further suppressed autophagy and concomitantly upregulated inflammatory factors (P < 0.05). Collectively, the findings revealed that RGS10 suppresses the inflammatory response and bone destruction through TFEB-mediated autophagy in apical periodontitis.

Targeting hexokinase 1 alleviates NLRP3-mediated inflammation in apical periodontitis: A laboratory investigation.

The aim of the study was to explore whether hexokinase 1 (HK1) is involved in the inhibition of inflammation mediated by nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) signalling pathway in the development of apical periodontitis (AP). Human AP tissues and normal control tissues were collected in the clinic. First, the levels of glucose, pyruvate, lactate and hexokinase activity were examined in human AP tissues. ECAR and OCR were further measured to detect the level of glycolysis in vitro model of inflammation, which established with lipopolysaccharide (LPS)-stimulated RAW264.7 cell line. Secondly, the expression of HK1, NLRP3, caspase-1 and interleukin (IL)-1β were measured by Western blot, immunohistochemistry or RT-qPCR. Finally, lentiviral short hairpin RNA (shRNA) silencing technique or the inhibitor 2-deoxy-d-glucose (2-DG) were used to further detect the relationship between HK1-mediated glycolysis and NLRP3-mediated inflammation in the development of AP in vitro. Initially, the level of glycolysis was significantly increased in human AP tissues. Subsequently, the expression of HK1, NLRP3, caspase-1 and IL-1β were upregulated significantly in human AP tissues. Furthermore, in the model of AP in vitro, a high level of glycolysis and the high expression of HK1, NLRP3, caspase-1 and IL-1β was observed. Finally, the expression of NLRP3, caspase-1 and IL-1β mediated by LPS stimulation was significantly reduced via HK1 knockdown or 2-DG treatment in vitro. Our data support that HK1-mediated glycolysis plays a crucial role in the development of AP via upregulating the NLRP3 signalling pathway. Moreover, targeting HK1 may contribute to prevent the progression of AP, which has a potential clinical translation.

MicroRNAs Markedly Expressed in Apical Periodontitis Cooperatively Regulate Cytokines and Growth Factors Promoting an Anti-inflammatory Response

IntroductionMicroRNAs have been shown to play a role in the pathogenesis of apical periodontitis. Upregulation of miR-10a-5p and downregulation of miR-891a-5p were previously reported in apical periodontitis samples. This study aims to perform a functional characterization of miR-10a-5p, investigating its capacity to regulate the expression of inflammatory cytokines and growth factors, as well as a possible co-regulation mechanism with miR-891a-5p in the development of apical periodontitis. MethodsmiR-10a-5p mimics/controls and miR-891a-5p inhibitors/controls were introduced to human K-562 cells in the presence or absence of lipopolysaccharide. Total RNA was extracted from cell lysates, and target genes were examined via quantitative reverse transcription-polymerase chain reaction. Cell lysates were also subjected to proteomics analysis. Furthermore, mimics of miR-10a-5p and inhibitors of miR-891a-5p were co-transfected into K-562 cells. RNA sequencing and quantitative reverse transcription-polymerase chain reaction were carried out to examine their target genes. ResultsOverexpression of miR-10a-5p led to downregulation of tumor necrosis factor-alpha and interleukin-1 beta mRNA and upregulation of transforming growth factor-beta 1 (TGFB1) mRNA expression, whereas interleukin 3 and TGF-β1 proteins were upregulated. Simultaneous overexpression of miR-10a-5p and inhibition of miR-891a-5p further increased TGFB1 mRNA transcript levels. RNA sequencing revealed that genes co-regulated by miR-10a-5p and miR-891a-5p may be involved in apical periodontitis-related pathways such as tumor necrosis factor, transient receptor potential, and vascular endothelial growth factor signaling pathways. ConclusionsmiR-10a-5p may modulate the expression of multiple inflammatory cytokines and growth factors such as tumor necrosis factor-alpha, IL-1β, interleukin 3, and TGF-β1. In addition, miR-10a-5p and miR-891a-5p cooperatively regulate TGFB1 gene expression, and the gene network of this co-regulation is integrated with many pathways in apical periodontitis.

Порівняльний аналіз ефективності сучасних методів активації іригантів у протоколі хемо-механічної обробки системи кореневого каналу (огляд літератури)

Resume. Development of apical periodontitis is the most common complication of unsuccessful endodontic treatment. Cleaning the root canal system is a crucial stage and the main factor for a successful endodontic protocol. Inability to remove debris from inaccessible branches of the root canal system, especially from the apical region, leads to and increases the risk of secondary infection. Selection of the optimal method for activating irrigants remains a current issue. According to the results of several studies, none of the individual irrigation activation techniques allows achieving ideal cleanliness in the root canal, but the use of laser, sonic, multisonic, and ultrasonic activation significantly improves the quality of cleaning and provides a prolonged antimicrobial effect by enhancing the diffusion of intracanal antiseptics, their hydrolytic and antibacterial effectiveness, which will eventually ensure maximum adhesion of filling materials. This, in turn, indicates the absence of a unified protocol that would provide stable irrigation efficiency and long-term results in endodontic treatment. The use of a protocol with combined activation of irrigants remains an open question among clinicians and scientists. Key words: endodontics, root canal, irrigation, activation, Sodium hypochlorite, smear layer, debris, ultrasonic, sonic activation, laser, Gentlewave, SAF (Self-Adjusting File), XP-Endo Finisher.

Comparison of the biomechanical differences in the occlusal movement of wild-type and BMP9 knockout mice with apical periodontitis.

Apical periodontitis is a common clinical disease caused by bacteria; bacterial metabolites can cause an imbalance in bone homeostasis, bone mass reduction, and tooth loss. Bone resorption in apical periodontitis causes a concentration of stress in the tooth and periodontal tissues during occlusion, which aggravates the disease. Emerging evidence indicates that bone morphogenetic protein 9 (BMP9), also known as growth differentiation factor 2(Gdf2), may play an important role in tooth and dentoalveolar development. Herein, we investigated the role of BMP9 in the development of apical periodontitis and its effects on the biomechanics of dentoalveolar bone. Apical periodontitis models were established in five BMP9 knockout (KO) mice and five C57BL/6 WT (wild-type) mice. At baseline and 14, 28, and 42days after modeling, in vivo micro-computed tomography analysis and three-dimensional (3D) reconstruction were performed to evaluate the apical lesion in each mouse, and confirm that the animal models were successfully established. Finite element analysis (FEA) was performed to study the stress and strain at the alveolar fossa of each mouse under the same vertical and lateral stress. FEA revealed that the stress and strain at the alveolar fossa of each mouse gradually concentrated on the tooth cervix. The stress and strain at the tooth cervix gradually increased with time but were decreased at day 42. Under the same lingual loading, the maximum differences of the stress and strain at the tooth root in KO mice were greater than those in WT mice. Thus, these findings demonstrate that BMP9 could affect the biomechanical response of the alveolar fossa at the tooth root in mice with apical periodontitis. Moreover, the effects of BMP9 on the biomechanical response of the alveolar bone may be site-dependent. Overall, this work contributes to an improved understanding of the pathogenesis of apical periodontitis and may inform the development of new treatment strategies for apical periodontitis.

Leukotriene B4 Loaded in Microspheres Inhibits Osteoclast Differentiation and Activation.

To investigate osteoclast formation in vivo and if leukotriene B4 (LTB4) loaded in microspheres (MS) could be used as a therapeutical strategy to promote a sustained delivery of the mediator and prevent osteoclast differentiation. Methods: In vivo, apical periodontitis was induced in mice to investigate osteoclast differentiation and signaling in absence of 5-lipoxygenase (5-LO). In vitro, LTB4-MS were prepared using an oil-in-water emulsion solvent extraction-evaporation process. Characterization and efficiency of LTB4 encapsulation were investigated. J774A.1 macrophages were cultured in the presence of monocyte colony-stimulating factor (M-CSF) and ligand for receptor activator of nuclear factor kappa B (RANKL) and then stimulated with LTB4-MS. Cytotoxicity, in vitro MS-LTB4 uptake, osteoclast formation and gene expression were measured. Results: We found that 5-LO negatively regulates osteoclastic formation in vivo during apical periodontitis development. In vitro, LTB4-MS were up-taken by macrophages and were not cytotoxic to the cells. LTB4-MS inhibited osteoclast formation and the synthesis of osteoclastogenic genes Acp5, Mmp9, Calcr and Ctsk. LTB4-MS inhibited differentiation of macrophages into an osteoclastic phenotype and cell activation under M-CSF and RANKL stimulus.

Revisiting the role of IL-1 signaling in the development of apical periodontitis.

Apical periodontitis (AP) develops as a result of an immune response to pulpal bacterial infection, and various cytokines are involved in the pathogenesis of AP, with Interleukin (IL)-1 being considered a key cytokine. The role of IL-1 in the pathogenesis of AP has been well studied. It is known that IL-1 expression in periapical lesions correlates closely with the development of AP. IL-1 is a potent bone-resorptive cytokine that induces osteoclast formation and activation. Hence, inhibiting its signaling with IL-1 receptor antagonist (IL-1RA) results in a reduction in periapical lesion size. On the other hand, IL-1 is also a central cytokine that combats bacterial infection by activating innate immune responses. Therefore, a complete loss of IL-1 signaling leads to a failure to limit bacterial dissemination and consequently exacerbates AP. In vivo, IL-1 expression is tightly regulated and its signaling is modulated to optimize the immune response. Obesity causes systemic low-grade chronic inflammation and increases the risk of cardiovascular, renal, and other disorders. In experimentally induced AP, obesity significantly increases periapical bone loss, albeit the underlying mechanism remains unclear. Recent technological innovations have enabled more comprehensive and detailed analyses than previously, leading to new insights into the role of IL-1RA in regulating IL-1 signaling, and modulating apical lesion progression in obesity. In this review, we provide a brief overview of the function of IL-1 in AP development, with special emphasis on the latest findings in normal weight and obese states.

Single nucleotide polymorphisms as a predisposing factor for the development of apical periodontitis-An umbrella review.

The interaction between heredity and different environmental factors in the modification of apical periodontitis (AP) susceptibility and prediction of its progression remain poorly elucidated. This umbrella review aimed to (i) analyse the available relevant systematic reviews in an attempt to determine the association between genotype and allelic distribution of different single-nucleotide polymorphisms (SNPs) and the development of AP, (ii) report deficiencies and gaps in knowledge in this area and (iii) present recommendations to conduct future clinical studies and systematic reviews. A literature search was conducted using Clarivate Analytics' Web of Science, Scopus, PubMed and Cochrane Database of Systematic Reviews, from inception to October 2021, with no language restrictions, including a grey literature search. Systematic reviews with/without meta-analysis evaluating genotype and allelic distribution of different SNPs between adult patients with/ without AP were included. All other type of studies were excluded. The methodological quality was assessed using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR)-2 tool. Two independent reviewers were involved in study selection, data extraction and appraising the included reviews; disagreements were resolved by a third reviewer. The current study includes five systematic reviews. Three reviews performed meta-analysis. Three reviews were graded by AMSTAR 2 as 'critically low' quality, whereas the other two were graded as 'low' and 'moderate' quality. Two reviews indicated that carriers of specific genotypes and alleles of tumour necrosis factor-alpha (TNF-α) -308 G > A and interleukin 1-beta (IL-1β) + 3954 C/T gene polymorphisms are more susceptible to an acute and persistent form of AP. However, high heterogeneity was observed. The statistical heterogeneity within included systematic reviews was a consequence of clinical and methodological diversity amongst primary studies. Although some of the included reviews suggested that carriers of specific genotype and/or allele of TNF-α -308 G > A and IL-1β + 3954 C/T SNPs are more susceptible to AP, their conclusions should be interpreted with caution. No candidate genes could be identified as a definitive genetic risk or protective factor for the development and progression of AP, and further high-quality genome-wide association studies are warranted.

Chronic systemic corticosteroid therapy influences the development of pulp necrosis and experimental apical periodontitis, exacerbating the inflammatory process and bone resorption in rats.

The main aim of the study was to evaluate the inflammatory response and development of apical periodontitis in rats chronically treated with glucocorticoids. Male Wistar rats (Rattus novergicus) were randomly divided into two groups: the experimental group, which was treated with prednisone (5mg/kg/day) and a control group, which was administered saline solution for 30days before induction of apical periodontitis, continuing until the day of euthanasia days 0, 7, 14 and 28 after injury induction. The mandibles were subjected to histological evaluation to determine the size of the lesion, was also performed for the presence and absence of pulp necrosis, bone resorption and micro abscesses, and histomorphometric analyses were performed based on the number of polymorphonuclear cells and mononuclear cells. Histochemical analysis was also performed to assess the percentage of collagen fibres and their typification, in addition to immunohistochemistry for the inflammatory markers interleukin IL-1β, IL-6, TNF-α and TRAP. Despite after 7days, there was no differences between groups, a significant increase in the root pulp necrosis (p=.001), micro-abscesses (p=.026) and the size of the apical lesion on the 14th day of treatment with prednisone (p=.008). On the same day, there was also an increase in the number of polymorphonuclear cells (p=.042) and cells immunostained for IL-1β (p=.006), IL-6 (p<.001) and TRAP (p=.002) in animals treated with prednisone. The numbers of mononuclear cells also increase in 28days (p=.025) and TNF-α ± increases in the prednisone group on the 7th day (p=.041). The prednisone group also showed a decrease in collagen after 14 (both type I [p=.041] and type III [p=.046]) and 28 type III (p=.002) days after the coronary opening. The glucocorticoids modified the development of experimental apical periodontitis induced in rats, causing an early increase in periapical bone resorption and pulp necrosis. These effects are associated with alterations in cytokine levels, in the inflammatory response and in collagen deposition, in the 14th day after injury induction.