Pathogenesis Of Apical Periodontitis Research Articles

The importance of mechanosensitive cell mediated prostaglandin and nitric oxide synthesis in the pathogenesis of apical periodontitis: comparative with chronic periodontitis

ObjectivesMechano-sensitive odontoblast cells, which sense mechanical loading and various stresses in the tooth structure, synthesize early signaling molecules such as prostaglandin E2 (PGE2) and nitric oxide (NO) as an adaptive response. It is thought that these synthesized molecules can be used for the diagnosis and treatment of periodontal and periapical diseases. The aim of this study was to investigate the relationship between the severity of apical periodontitis (AP) and chronic periodontitis (CP) and serum (s) TNF-α, IL-10, PGE2 and NO levels, as well as PGE2 and NO levels in gingival crevicular fluid (GCF) samples.Materials & methodsA total of 185 subjects were divided into three categories: AP group (n = 85), CP group (n = 50) and healthy control group (n = 50). The AP group was divided into 3 subgroups according to abscess scoring (AS-PAI 1, 2 and 3) based on the periapical index. The CP group was divided into 4 subgroups according to the periodontitis staging system (PSS1, 2,3 and 4). After recording the demographic and clinical characteristics of all participants, serum (s) and gingival crevicular fluid (GCF) samples were taken. TNF-α, IL-10, PGE2 and NO levels were measured in these samples.ResultsUnlike serum measurements (sTNF-α, sIL-10, sNO and sPGE2), GCF-NO and GCF-PGE levels of the AP group were significantly higher than the control group in relation to abscess formation (54.4 ± 56.3 vs. 22.5 ± 12.6 µmol/mL, p < 0.001 and 100 ± 98 vs. 41 ± 28 ng/L, p < 0.001, respectively). Confirming this, the GCF-NO and GCF-PGE levels of the AS-PAI 1 group, in which abscesses have not yet formed, were found to be lower than those in AS-PAI 2 and 3, which are characterized by abscess formation [(16.7(3.7-117.8), 32.9(11.8-212.8) and 36.9(4.3-251.6) µmol/mL, p = 0,0131; 46.0(31.4–120.0), 69.6(40.3-424.2) and 74.4(32.1–471.0) ng/L, p = 0,0020, respectively]. Consistent with the increase in PSS, the levels of sTNF [29.8 (8.2-105.5) vs. 16.7(6.3–37.9) pg/mL, p < 0.001], sIL-10 [542(106–1326) vs. 190(69–411) pg/mL, p < 0.001], sNO [182.1(36.3–437) vs. 57.0(15.9–196) µmol/mL, p < 0.001], sPGE2 [344(82-1298) vs. 100(35-1178) ng/L, p < 0.001], GCF-NO [58.9 ± 33.6 vs. 22.5 ± 12.6 ng/L, p < 0.001] and GCF-PGE2 [ 99(37–365) vs. 30(13–119), p < 0.001] in the CP group were higher than the control group. Comparison ROC analysis revealed that the GCF-PGE2 test had the best diagnostic value for both AP and CP (sensitivity: 94.1 and 88.0; specificity: 64.0 and 78.0, respectively; p < 0.001).ConclusionsGCF-PE2 and GCF-NO have high diagnostic value in the determination of AP and CP, and can be selected as targets to guide treatment. In addition, the measurements of PGE2 and NO in GCF can be used as an important predictor of pulpal necrosis leading to abscess in patients with AP.Clinical relevanceIn this article, it is reported that syntheses of early signaling molecules such as PGE2 and NO can be used for the diagnosis and treatment target of periapical and periodontal infections.

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 Role of Macrophage Efferocytosis in the Pathogenesis of Apical Periodontitis.

Macrophages (Mφs) play a crucial role in the homeostasis of the periapical immune micro-environment caused by bacterial infection. Mφ efferocytosis has been demonstrated to promote the resolution of multiple infected diseases via accelerating Mφ polarization into M2 type. However, the Mφ efferocytosis-apical periodontitis (AP) relationship has not been elucidated yet. This study aimed to explore the role of Mφ efferocytosis in the pathogenesis of AP. Clinical specimens were collected to determine the involvement of Mφ efferocytosis in the periapical region via immunohistochemical and immunofluorescence staining. For a further understanding of the moderator effect of Mφ efferocytosis in the pathogenesis of AP, both an in vitro AP model and in vivo AP model were treated with ARA290, a Mφ efferocytosis agonist. Histological staining, micro-ct, flow cytometry, RT-PCR and Western blot analysis were performed to detect the inflammatory status, alveolar bone loss and related markers in AP models. The data showed that Mφ efferocytosis is observed in the periapical tissues and enhancing the Mφ efferocytosis ability could effectively promote AP resolution via facilitating M2 Mφ polarization. Collectively, our study demonstrates the functional importance of Mφ efferocytosis in AP pathology and highlights that accelerating Mφ efferocytosis via ARA290 could serve as an adjuvant therapeutic strategy for AP.

Metformin switches cell death modes to soothe the apical periodontitis via ZBP1.

Apical periodontitis (AP) is a disease caused by pathogenic microorganisms and featured with the degradation of periapical hard tissue. Our recent research showed the crucial role of Z-DNA binding protein 1 (ZBP1)-mediated necroptosis and apoptosis in the pathogenesis of AP. However, the specific regulatory mechanisms of ZBP1 in AP are not fully elucidated. It was found that metformin has a regulatory role in cell necroptosis and apoptosis. But whether and how metformin regulates necroptosis and apoptosis through the ZBP1 in the context of AP remains unknown. This study provided evidence that lipopolysaccharide (LPS) promotes the synthesis of left-handed Z-nucleic acids (Z-NA), which in turn activates ZBP1. Knockout of Zbp1 by CRISPR/Cas9 technology significantly reduced LPS-induced necroptosis and apoptosis invitro. By using Zbp1-knockout mice, periapical bone destruction was alleviated. Moreover, type I interferon induced the expression of interferon-stimulated genes (ISGs), which serve as a major source of Z-NA. In addition, the RNA-editing enzyme Adenosine Deaminase RNA specific 1 (ADAR1) prevented the accumulation of endogenous Z-NA. Meanwhile, metformin suppressed the ZBP1-mediated necroptosis by inhibiting the expression of ZBP1 and the accumulation of ISGs. Metformin also promoted mitochondrial apoptosis, which is critical for the elimination of intracellular bacterial infection. The enhanced apoptosis further promoted the healing of infected apical bone tissues. In summary, these results demonstrated that the recognition of Z-NA by ZBP1 plays an important role in AP pathogenesis. Metformin suppressed ZBP1-mediated necroptosis and promoted apoptosis, thereby contributing to the soothing of inflammation and bone healing in AP.

Relationship of MMP-9 with the clinical course of apical periodontitis and the main bacterial species in the oral microbiota.

Bacterial products, host immune cells and cytokines have been reported to play an important role in the pathogenesis of apical periodontitis (AP). This study aimed to determine the main bacterial species in the microbiota as gram positive and negative and to compare the relationship between matrix metalloproteinase (MMP)-9 and tumor necrosis factor (TNF)-α with controlled patient groups. 60 patients with AP and extraction indication were included in the study. 30 systemically healthy volunteers without AP were selected as the control group. After access cavity preparation, an initial microbiologic sample (S1) was taken from the root canal. After atraumatic extraction of the tooth, a second microbial sample (S2) was taken from the extraradicular region. After bacterial DNA extraction, 16S rRNA gene primer was designed for sequence analysis. Bacterial community profiling was made by Sanger sequencing of the PCR products. In addition, serum MMP-9 and TNF-α levels were measured from all patients. TNF-α levels of the AP group were higher than the control group, while MMP-9 levels were found to be lower (p = 0.0264 and p = 0.0146, respectively). There was no difference in the main bacterial species isolated from the samples taken from the intracanal and extraradicular region of the tooth with AP (p = 0.714). The main bacterial species in the intracanal region of the tooth with AP are similar to the main bacterial species in the extraradicular region. The pathophysiology of the tooth with AP is associated with low MMP-9 and high TNF-α, independent of the bacterial species in the intracanal and extraradicular regions.

A Case of Respiratory Epithelium-Lined Cyst with Enriched Nociceptor Innervation

Apical lesions of endodontic origin can be classified as either granulomas or cysts. In rare cases, respiratory epithelium can proliferate and encapsulate a lesion, forming a cyst. Moreover, the innervation of apical lesions has only been previously reported in animal models of apical periodontitis. This report demonstrates an unusual case in which tooth #15 was initially treated with nonsurgical root canal therapy. Still, the patient remained in moderate to severe pain for several days following the procedure. Next, an intentional replantation was performed in which a periapical cyst was curetted from the alveolus. The patient experienced immediate pain relief following the procedure. Histological analysis revealed that the periapical cyst was lined entirely with respiratory epithelium, and immunohistochemical analysis showed it to be densely innervated. In addition, these nerve fibers expressed the LPS receptor, TLR4. This is the first demonstration of the innervation pattern of a periapical cyst. Further studies are warranted to evaluate innervation in apical lesions and its correlation with pre- and intra-operative symptoms and their participation in the pathogenesis of apical periodontitis.

Neutrophil Extracellular Traps Aggravate Apical Periodontitis by Stimulating Osteoclast Formation

IntroductionNeutrophil extracellular traps (NETs) have been described as structures composed of DNA and proteins, such as elastase and myeloperoxidase, that are able to kill bacteria extracellularly. The aim of the present study was to evaluate the role of NETs in bone resorption observed in pulp infection–induced apical periodontitis in mice. MethodsApical periodontitis was experimentally induced by exposing the dental pulp of the mandibular first molar of mice to the oral microenvironment. The expression of NETs was evaluated by immunofluorescence in mice and biopsies of apical periodontitis. Mice were treated with vehicle or DNase I to degrade NETs, and the samples were collected after 7 days. The size of the apical lesion and the osteoclast number were determined in hematoxylin-eosin– and tartrate-resistant acid phosphatase–stained sections, respectively. Osteoclast differentiation and function markers were evaluated by quantitative polymerase chain reaction. The level of NETs in the serum was determined by the myeloperoxidase-DNA PicoGreen assay. ResultsWe first confirmed the presence of neutrophils and NETs at the site of the lesion in mice and in biopsies of patients with apical periodontitis. The treatment of mice with DNase I reduced the level of NETs in the serum and led to a reduction in apical lesion size and alveolar bone resorption. This effect was associated with a reduction of local inflammatory infiltrate and a reduced number of osteoclasts. We found that the increased expression of Acp5, Ctsk, and Rankl genes associated with osteoclast formation and function were abrogated by the absence of NETs. ConclusionsOur data highlight NETs as an important player in the pathogenesis of apical periodontitis with regard to the local inflammation and consequent bone resorption after pulp infection.

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.

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.

Evolution of endodontic medicine: a critical narrative review of the interrelationship between endodontics and systemic pathological conditions.

Endodontics has gained emphasis in the scientific community in recent years due to the increase in clinical and in animal models studies focused on endodontic medicine, which aims to evaluate the interrelationship between systemic and periapical tissues pathological conditions. These studies have shown that systemic changes can boost the pathogenesis of endodontic infection, favoring its development and progression. A contrary relationship is reported in numerous studies that affirm the potential of endodontic infection to trigger systemic damage and may lead to the worsening of pre-existing pathologies. Recently, the potential of filling materials to develop systemic changes such as neurological alterations had been evaluated, also showing that systemic diseases can negatively influence tissue responses to filling materials after endodontic treatment. Despite advances in endodontic medicine studies, there are still gaps in knowledge on the mechanisms of interactions between apical periodontitis (AP) and systemic diseases and much research to be done. In this sense, this critical narrative literature review aimed to show the evolution of studies in endodontic medicine to help the endodontist to know the role of systemic diseases in the pathogenesis of AP and the possible interference in the repair of periapical tissues after endodontic treatment, as well as to evidence the systemic complications that can be triggered or aggravated in the presence of endodontic infection.

The possible role of sirtuin 5 in the pathogenesis of apical periodontitis.

We investigated the relation between expression of sirtuin 5 (SIRT5) in osteoblastic cells and progression of apical periodontitis. The role of SIRT5 in hypoxia-induced reactive oxygen species (ROS) formation and osteoblast apoptosis was also examined. Progression of rat apical periodontitis was monitored by conventional radiography and microcomputed tomography. SIRT5 and oxidative stress biomarker 8-OHdG in bone-lining cells were assessed by immunohistochemistry. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was used to demonstrate apoptosis. In primary human osteoblasts cultured under hypoxia, Western blot was used to analyze SIRT5 expression and cleavage of pro-caspase 3 and poly(ADP-ribose) polymerase (PARP). SIRT5 was overexpressed through lentiviral technique. ROS formation and mitochondrial membrane potential changes were assessed by MitoSOX-Red and JC-1 fluorescence, respectively. Immunofluorescence microscope was used to evaluate mitochondrial release of cytochrome c. In rat apical periodontitis, disease progression was accompanied by decreased expression of SIRT5, increased oxidative stress, and enhanced apoptosis in bone-lining cells. SIRT5 was suppressed in cultured osteoblasts under hypoxia. SIRT5 overexpression ameliorated hypoxia-enhanced ROS formation, mitochondrial depolarization, cytochrome c leakage, activation of caspase-3, and PARP fragmentation. SIRT5 is able to alleviate hypoxia-enhanced osteoblast apoptosis. SIRT5 augmentation may have therapeutic potential for apical periodontitis.

Inhibition of the CXCL9-CXCR3 axis suppresses the progression of experimental apical periodontitis by blocking macrophage migration and activation

Apical periodontitis (AP) is an acute or chronic inflammatory disease caused by complex interactions between infected root canal and host immune system. It results in the induction of inflammatory mediators such as chemokines and cytokines leading to periapical tissue destruction. To understand the molecular pathogenesis of AP, we have investigated inflammatory-related genes that regulate AP development. We found here that macrophage-derived CXCL9, which acts through CXCR3, is recruited by progressed AP. The inhibition of CXCL9 by a CXCR3 antagonist reduced the lesion size in a mouse AP model with decreasing IL-1β, IL-6 and TNFα expression. The treatment of peritoneal macrophages with CXCL9 and LPS induced the transmigration and upregulation of osteoclastogenic cytokines such as IL-1β, IL-6 and matrix metalloprotease 2, a marker of activated macrophages. This suggests that the CXCL9-CXCR3 axis plays a crucial role in the development of AP, mediated by the migration and activation of macrophages for periapical tissue destruction. Our data thus show that CXCL9 regulates the functions of macrophages which contribute to AP pathogenesis, and that blocking CXCL9 suppresses AP progression. Knowledge of the principal factors involved in the progression of AP, and the identification of related inflammatory markers, may help to establish new therapeutic strategies.

Blockade of fatty acid signalling inhibits lipopolysaccharide-induced macrophage recruitment and progression of apical periodontitis.

To examine the role of palmitic acid in lipopolysaccharide (LPS)-stimulated chemotaxis of macrophages and the potential contribution of saturated fatty acid in signalling during the pathogenesis of apical periodontitis. J774, a mouse macrophage cell line, was used in the experiments. After treatment with LPS, proteolytic maturation of sterol regulatory element-binding protein-1c (SREBP-1c) and expression of fatty acid synthase (FASN) were examined by Western analysis. Levels of palmitic acid were measured by reverse phase-high performance liquid chromatography-mass spectrometry. Knockdown of SREBP-1c and FASN was accomplished by small interfering RNA technology. Secretion of CC-chemokine ligand 2 (CCL2) and cellular chemotaxis were assessed by enzyme-linked immunosorbent assay and transwell migration assay, respectively. Sulfo-N-succinimidyl oleate (SSO) treatment was used to inhibit fatty acid signalling in vitro and also in a rat model of apical periodontitis. All data were first subjected to Levene's test. In vitro data were then analysed using ANOVA followed by Tukey's multiple comparison test. Data from animal experiments were analysed by independent t-tests. The significant level was set at 0.05. LPS stimulated proteolytic maturation of SREBP-1c and FASN expression in macrophages and significantly enhanced palmitic acid synthesis (P<0.05). Knockdown of SREBP-1c attenuated LPS-enhanced FASN expression. Knockdown of FASN significantly suppressed LPS-enhanced palmitic acid synthesis (P<0.05). LPS and exogenous palmitic acid significantly enhanced CCL2 secretion and macrophage chemotaxis (all P<0.05). Inhibition of FASN expression significantly alleviated LPS-augmented CCL2 secretion (P<0.05). SSO significantly suppressed CCL2 secretion and macrophage chemotaxis augmented by LPS and palmitic acid (all P<0.05). In a rat model of induced apical periodontitis, SSO treatment significantly attenuated progression of apical periodontitis and macrophage recruitment (all P<0.05). LPS/SREBP-1c/FASN/palmitic acid signalling contributed to tissue destruction caused by bacterial infection. Modulation of lipid metabolism and signalling may be helpful for the management of apical periodontitis.

MicroRNAs: emerging players in apical periodontitis.

Apical periodontitis is an inflammatory disorder of periradicular tissues developed from endodontic infections. Understanding its pathophysiology and the underlying molecular mechanisms is key to the advancement of endodontics. MicroRNAs (miRNAs), a group of evolutionarily conserved small non-coding RNAs, may be phenotypically and functionally associated with the pathogenesis of apical periodontitis. Several studies have focused on the role of miRNAs in the pulp and periradicular biology, and they have demonstrated their essential functions, such as initiating odontogenic differentiation and promoting pro- or anti-inflammatory responses in pulpitis. Up to date, over 2,000 miRNAs have been discovered in humans; however, only few have been reported to associate with apical periodontitis. Therefore, identifying miRNAs involved in diseased apical tissues and conducting functional studies are important in expanding our current knowledge of pulp and periradicular biology and exploring novel therapeutic avenues. In this review, we revisit current models of apical periodontitis and miRNA biogenesis, analyze existing evidence of the involvement of miRNAs in diseased apical tissues, and discuss their diverse functions and potential values. Based on their sheer abundance, prolonged stability in biofluid, and relative ease of sampling, miRNAs may be a useful tool to be developed as diagnostic biomarkers for apical periodontitis. Furthermore, it can be used as therapeutic targets in conjunction with conventional endodontic therapies.

Metaloproteinases da matriz: papel no desenvolvimento das lesões periapicais e modulação após tratamento endodôntico

Introduction: Apical periodontitis represents a local immune response directed against the progression of microorganisms from the dental pulp to the apical foramen and periapical tissues, which results in bone and dental resorption. The aim of this review is to describe the expression of this group of proteases in apical periodontitis and its modulation during the periapical healing phase following root canal treatment. Literature review: The pathogenesis of apical periodontitis involves degradation of several extracellular matrix components. Matrix metalloproteinases (MMPs) are expressed in response to specific stimuli by resident cells of connective tissue during tissue remodeling and by inflammatory cells that arrive into the surrounding tissues during inflammatory events. MMPs have been reported in apical periodontitis, either experimentally induced or obtained from humans and there is evidence that these enzymes show diff erent expression patterns in granulomas and periapical cysts. Root canal therapy is important for the reduction of periapical inflammation as well as the synthesis of MMPs, especially when using a calcium hydroxide-based dressing. Conclusion: Apical periodontitis show high expression of matrix metalloproteinases and root canal treatment results in less expression of MMPs when compared to untreated apical periodontitis.

Herpesviral-bacterial synergy in the pathogenesis of apical periodontitis: New insights and future perspectives

Herpesviral-bacterial synergy in the pathogenesis of apical periodontitis: New insights and future perspectives

Distribution of Rothia species in root canals in a Japanese population

Rothia species are components of the normal oral microflora, which have been recognized as emerging opportunistic pathogens in immune compromised hosts. This study was performed to investigate the distribution of Rothia species in infected root canals. The correlations of clinical findings with the presence of Rothia species were also evaluated. A total of 200 root canal samples, including 92 primary infections and 108 secondary infections, were collected from 200 Japanese patients. Polymerase chain reaction (PCR) targeting the 16S rRNA gene was performed to detect three Rothia species, i.e., Rothia mucilaginosa, Rothia aeria, and Rothia dentocariosa. The detection frequencies of R. mucilaginosa, R. aeria, and R. dentocariosa were 49/200 (24.5%), 95/200 (47.5%), and 55/200 (27.5%), respectively. There were no significant differences in the detection frequencies between primary and secondary endodontic infections. The detection frequency of R. mucilaginosa in cases with gingival swelling was 42.9%, and there were significantly more cases positive than negative for this species (P = 0.042). The presence of R. aeria also showed correlations with radiolucency around the root apex (P = 0.001) and pain on percussion (P = 0.044). Quantitative real-time PCR revealed that the relative abundance of R. mucilaginosa in total bacterial counts ranged from 0.04% to 91.8%. These results indicated that Rothia species colonize root canals at relatively high frequency, and that root canals are potential reservoirs of these pathogens. The results also suggest that Rothia species are involved in the pathogenesis of apical periodontitis.

Current trends of genetics in apical periodontitis research.

Genetics is an emerging topic in endodontic research focusing on the host response regarding the pathogenesis of apical periodontitis (AP). A number of genetic epidemiological studies carried out by many investigators worldwide have shown evidence of an association between certain candidate genes and AP. Some studies have been conducted on knockout mice with a deficiency in certain proteins, leading to more or less severe AP, and thus suggesting a pivotal role of these genes in AP pathogenesis. Other research has evaluated the association between genetic polymorphisms in humans with different AP aspects; these studies pointed out that genetic polymorphisms in some candidate genes are involved in inter-individual variations in their response to AP. Therefore, the objective of this report was to provide an updated overview of the genes involved in AP pathogenesis, with a focus on the most relevant candidate genes.

Expression of SOCS-1 and SOCS-3 in chronic periapical lesions and its clinical significance

To detect the expression of suppressor of cytokine signaling-1 (SOCS-1) and suppressor of cytokine signaling-3 (SOCS-3) in chronic periapical lesions and to clarify their roles in pathogenesis of apical periodontitis. A total of 25 chronic periapical lesion tissues and 16 normal periodontal ligament tissues were collected respectively. The expression of mRNA was measured by real-time PCR, the protein expression was measured by immunohistochemical analysis. Statistical analysis was performed using SPSS 13.0 software package. Immunohistochemical results indicated that expression levels of SOCS-1 and SOCS-3 protein in chronic periapical lesions were significantly higher than that in normal tissues (P<0.01); Moreover, SOCS-1 and SOCS-3 protein expression levels in severe inflammation group were significantly higher than that in mild inflammation group (P<0.01). In mild inflammation group, severe inflammation group and control group, the expression levels of SOCS-1 mRNA were 2.620±1.552, 2.373±1.083 and 1.277±1.040, whereas those of SOCS-3 were 9.308±5.901, 7.565±3.233 and 1.232±1.099, respectively. The expression levels of SOCS-1 mRNA and SOCS-3 mRNA are significantly higher both in mild inflammation group and severe inflammation group than that in control group (P<0.01), while no significant difference is found in mild and severe inflammation group.

Association of End-stage Renal Disease with Radiographically and Clinically Diagnosed Apical Periodontitis: A Hospital-based Study

IntroductionThe present study aimed to evaluate the prevalence of apical periodontitis (AP) and endodontic treatment in patients with end-stage renal disease (ESRD) as compared with patients with no history of ESRD. MethodsIn this cross-sectional study, 40 patients diagnosed with nondiabetic ESRD were included. The control group consisted of 40 age-matched and sex-matched healthy individuals. Digital panoramic radiographs were exposed on patients in both the experimental and control groups. The number of remaining teeth and the prevalence of nonsurgical and/or surgical root canal treatment were evaluated. Also, the presence of AP in all teeth and endodontically treated teeth (ETT) was recorded using the periapical index. Logistic regression was used to determine the possible association between ESRD and AP. ResultsAP in at least 1 tooth was found in 29 of the patients with ESRD (73%) and in 16 of the control patients (40%) (odds ratio [OR] = 3.9, P < .05). In 21 (52%) patients with ESRD in the experimental group, at least 1 ETT was diagnosed with AP. In the control group, 11 (28%) individuals had AP affecting at least 1 of the ETT (OR = 2.9, P < .05). Adjusted for the number of teeth and endodontic treatment, ESRD was significantly associated with the presence of AP (P < .05; OR = 2.6; 95% confidence interval, 1.43–4.8). Also, the number of teeth with AP was significantly associated with the urea serum level in the experimental group (P < .05, β coefficient = 4.35). ConclusionAP was significantly more prevalent in the experimental group. This may suggest that ESRD could possibly alter the pathogenesis of AP. However, these findings do not confirm the presence of any cause-and-effect relationship between these conditions. Also, considering the modifying effect of AP on urea serum level, the treatment of AP could be incorporated in the treatment planning of patients with ESRD.