Periapical Granulomas Research Articles

Immunohistochemical Analysis of Cyclooxygenase-2 and Tumor Necrosis Factor Alpha in Periapical Lesions

IntroductionThe purpose of this study was to evaluate the expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor alpha (TNF-α) in periapical granuloma (PG) and radicular cyst (RC) samples and to correlate it with the type of lesion, the intensity of the inflammatory infiltrate, and the thickness of the epithelial lining. MethodsA total of 51 cases of periapical lesions (25 PGs and 26 RCs) were subjected to morphologic analysis and immunohistochemical study. The anti–COX-2 and anti–TNF-α antibodies were applied using the immunoperoxidase technique. Data were analyzed by the Mann-Whitney test, Pearson chi-square test, Fisher exact test, and Spearman correlation. ResultsAnalysis of the inflammatory infiltrate revealed that 80% of PGs exhibited a grade III infiltrate as opposed to a 19% rate in RCs (P < .001). Morphologic evaluation of the epithelial thickness of RCs revealed the presence of atrophic epithelium in 73% of cases. The majority of PGs had a score of 1 for COX-2 immunoexpression (n = 14, 54%) and a score of 2 for TNF-α expression (n = 16, 64%), whereas in cases of RCs a score of 1 was more prevalent for COX-2 and TNF-α expression (n = 17, 65%). Significant differences in the expression scores of COX-2 and TNF-α were detected in periapical lesions (P < .001). ConclusionsBased on these findings, we emphasize that RCs and PGs have a similar expression of inflammatory mediators (COX-2 and TNF-α) although the secretion of TNF-α by macrophages and of COX-2 by several cells was higher in PGs, indicating a greater inflammatory response in these lesions.

Inflammatory cell expression of Toll-like receptor-2 (TLR2) within refractory periapical granuloma.

Background: Toll-like receptor-2 (TLR2) is highly important within the immune system. Characterization of the expression of TLR2 within inflammatory cells in periapical lesions could help in diagnosis and management of refractory cases. The aim of the study is identification of Toll-like receptor (TLR2) through immunohistochemical and immunofluroscence expression in inflammatory cells within refractory periapical granuloma cases. Methods: Eight cases of refractory periapical granuloma were selected out of 772 cases. Histological examination and immunohistochemical staining with polyclonal rabbit antihuman TLR2, monoclonal mouse antihuman CD38, CD68 and CD83 primary antibodies, as well as immunofluorescence staining with goat anti-rabbit TLR2, donkey anti-mouse CD38, CD68 and CD83 primary antibodies was conducted. Positive controls, negative controls and experimental sections with no primary antibody were included in the study. Qualitative analysis and double immunofluorescence technique was used to characterize the TLR + cells. Results: In periapical granuloma, lymphocytes (CD38 cells) expressed the most amount of TLR reactivity followed by macrophages (CD68 cells), and odontogenic epithelial cells. Neutrophils, red blood cells (RBCs) and collagen ground substance were negative to TLR2. Conclusion: TLR2 was highly expressed by lymphocytes and plasma cells indicative of their major role in the inflammatory process and antigen recognition in refractory periapical granuloma. Dendritic cells expressing TLR2 were low in number suggesting a minor role in sustaining these lesions.

Inflammatory cell expression of Toll-like receptor-2 (TLR2) within refractory periapical granuloma.

Background: Toll-like receptor-2 (TLR2) is highly important within the immune system. Characterization of the expression of TLR2 within inflammatory cells in periapical lesions could help in diagnosis and management of refractory cases. The aim of the study is identification of Toll-like receptor (TLR2) through immunohistochemical and immunofluroscence expression in inflammatory cells within refractory periapical granuloma cases. Methods: Eight cases of refractory periapical granuloma were selected out of 772 cases. Histological examination and immunohistochemical staining with polyclonal rabbit antihuman TLR2, monoclonal mouse antihuman CD38, CD68 and CD83 primary antibodies, as well as immunofluorescence staining with goat anti-rabbit TLR2, donkey anti-mouse CD38, CD68 and CD83 primary antibodies was conducted. Positive controls, negative controls and experimental sections with no primary antibody were included in the study. Qualitative analysis and double immunofluorescence technique was used to characterize the TLR + cells. Results: In periapical granuloma, lymphocytes (CD38 cells) expressed the most amount of TLR reactivity followed by macrophages (CD68 cells), and odontogenic epithelial cells. Neutrophils, red blood cells (RBCs) and collagen ground substance were negative to TLR2. Conclusion:TLR2 was highly expressed by lymphocytes and plasma cells indicative of their major role in the inflammatory process and antigen recognition in refractory periapical granuloma. Dendritic cells expressing TLR2 were low in number suggesting a minor role in sustaining these lesions.

The Role of Galectin-7 in Endothelial Cells of Periapical Granulomas, Radicular Cysts, and Residual Radicular Cysts

Objectives: Our aims were to assess the immunoexpression of galectin-7 in endothelial cells in periapical granulomas (PGs), radicular cysts (RCs), and residual radicular cysts (RRCs), and to correlate these with the intensity of the inflammatory infiltrate and thickness of the cystic epithelial lining.

Immunoexpression of Osteoclastogenic Proteins in Human Periapical Chronic Lesions

Objective: To investigate the role of RANKL, cathepsin K, IL-33, and OPG in the development of radicular cysts (RCs) and periapical granulomas (PGs).

Botryoid Odontogenic Cyst: a Case Report

A 57-year-old Asian, female patient with asymptomatic hyperthyroidism developed a multilocular, radiolucent lesion, of 4 years' evolution, in the anterior region of the mandible; the lesion was well delimited and associated with the roots of vital teeth #31, #32, and #33. Excisional biopsy was performed, and a hypothetical diagnosis of periapical granuloma was made. The histologic sections revealed fragments of the odontogenic cyst, covered by thin layers of squamous epithelium, with focal areas of acanthosis and the presence of thicker epithelial areas composed of clear cells. Hyalinization of the connective tissue close to the epithelial layer was observed. The final diagnosis was botryoid odontogenic cyst, a rare cyst. As this cyst is multilocular, complete removal is difficult, rendering a high possibility of recurrence, and thus, a correct diagnosis is important.

Increased interleukin 1\u03b1 and interleukin 1\u03b2 expression is involved in the progression of periapical lesions in primary teeth

BackgroundInterleukin 1 (IL-1) is involved in bone resorption. However, the role of IL-1 in periapical lesions characterized by periapical bone destruction in primary teeth has not yet been fully elucidated. This study aimed to detect the distribution and expression of IL-1 in periapical lesions in primary teeth and assess the relationship between the cytokines and the degree of inflammatory cell infiltration.MethodsA total of 106 chronic periapical lesions in primary teeth were harvested. Haematoxylin and eosin (H&E) staining was used to determine the histological type and the inflammatory cell infiltration grade (mild, moderate, and severe), and immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were used to detect the distribution and expression of IL-1α and IL-1β.ResultsOf the 106 chronic periapical lesion samples, there were 85 cases of periapical granuloma, accounting for 80.19% of the total samples, and 21 cases of radicular cysts, accounting for 19.81%; no cases of abscess were detected. Immunohistochemistry results showed that both IL-1α and IL-1β were expressed in periapical granulomas and cysts. ELISA results showed that IL-1α and IL-1β levels were higher in the periapical granuloma group than in the radicular cyst and normal control groups (P < 0.05). In the periapical granuloma group, IL-1α and IL-1β were detected at higher levels in the severe inflammatory cell infiltration subgroup than in the mild-inflammatory cell infiltration subgroup (P < 0.05), and IL-1β expression was also higher in the moderate inflammatory cell infiltration subgroup than in the mild inflammatory cell infiltration subgroup (P < 0.01). A significant positive correlation was observed between the protein expression levels of IL-1α and IL-1β and the inflammation grade in periapical granulomas from primary teeth (P < 0.05).ConclusionExpression levels of the cytokines IL-1α and IL-1β in periapical granulomas from primary teeth increased with increasing inflammatory severity and appeared to be a contributing factor to the progression of periapical lesions.

Comparative Expression of CD34, Intercellular Adhesion Molecule-1, and Podoplanin and the Presence of Mast Cells in Periapical Granulomas, Cysts, and Residual Cysts

IntroductionThe aim of the present study was to compare the immunoexpression of CD34, intercellular adhesion molecule-1 (ICAM-1), and podoplanin and the presence of mast cells with clinical, demographic, radiologic, and histologic features from periapical granulomas, periapical cysts, and residual cysts. MethodsThirty-one lesions (5 granulomas, 15 periapical cysts, and 11 residual cysts) were selected. Histologic sections in silanized slides were used for the immunohistochemical reactions. The analysis of the images was performed by using an optical microscope, and data were analyzed with 5% significance (P < .05). ResultsCysts presented atrophic and hyperplastic epithelium in 11 cases (35.5%) and 15 cases (48.8%), respectively (P > .05). The intensity of the inflammatory infiltrate was similar when comparing the 3 groups (P > .05). CD34 and podoplanin expression and the presence of mast cells were similar when comparing the 3 groups; ICAM-1 expression was more intense in granulomas than cysts (P < .05). There were no statistically significant differences associated with the expression of the evaluated markers according to the intensity of the inflammatory infiltrate. ConclusionsThere were no differences in the expression of CD34 and podoplanin and in the presence of mast cells when the 3 groups were compared. ICAM-1 expression was more common in periapical granulomas.

Porphyromonas endodontalis reactivates latent Epstein-Barr virus.

To determine whether Porphyromonas endodontalis can reactivate latent Epstein-Barr virus (EBV). The concentrations of short-chain fatty acids (SCFAs) in P.endodontalis culture supernatants were determined using high-performance liquid chromatography. A promoter region of BamHI fragment Z leftward open reading frame 1 (BZLF-1), which is a transcription factor that controls the EBV lytic cycle, was cloned into luciferase expression vectors. Then, the luciferase assay was performed using P.endodontalis culture supernatants. Histone acetylation using Daudi cells treated with P.endodontalis culture supernatants was examined using Western blotting. BZLF-1 mRNA and BamHI fragment Z EB replication activator (ZEBRA) protein were also detected quantitatively using real-time polymerase chain reaction (PCR) and Western blotting. Surgically removed periapical granulomas were examined to detect P.endodontalis, EBV DNA, and BZLF-1 mRNA expression using quantitative real-time PCR. Statistical analysis using Steel tests was performed. The concentrations of n-butyric acid in P.endodontalis culture supernatants were significantly higher than those of other SCFAs (P=0.0173). Using B-95-8-221 Luc cells treated with P.endodontalis culture supernatants, the luciferase assay demonstrated that P.endodontalis induced BZLF-1 expression. Hyperacetylation of histones was also observed with the culture supernatants. BZLF-1 mRNA and ZEBRA protein were expressed by Daudi cells in a dose-dependent manner after the treatment with P.endodontalis culture supernatants. P.endodontalis and BZLF-1 in periapical granulomas were also detected. The expression levels of BZLF-1 mRNA were similar to the numbers of P.endodontalis cells in each specimen. n-butyric acid produced by P.endodontalis reactivated latent EBV.

The Expression of Interferon Regulatory Factor 8 in Human Periapical Lesions

IntroductionInterferon regulatory factor 8 (IRF8) is a critical transcription factor in innate immune responses that regulates the development and function of myeloid cells. Human periapical lesions are caused by endodontic microbial infections. However, the presence of IRF8 in human periapical lesions remains elusive. This study aims to explore the expression of IRF8 in human periapical lesions and the possible association of IRF8 with macrophages, nuclear factor kappa B (NF-κB) signaling, and the autophagy process. MethodsThirty-nine human periapical tissues, including healthy control tissues (n = 15), radicular cysts (RCs, n = 11), and periapical granulomas (PG, n = 13), were examined. Tissues were fixed in paraformaldehyde and analyzed. The inflammatory infiltrates of lesions were evaluated by hematoxylin-eosin, and the expression of IRF8 was analyzed by immunohistochemistry. Double immunofluorescence assessment was performed to colocalize IRF8 with CD68, NF-κB p65, and LC3B. ResultsThe expression of IRF8 was significantly higher in RCs and PGs than in the healthy control group, but no significant difference was found between RCs and PGs. There were significantly more IRF8-CD68 double-positive cells in RCs and PGs than in the healthy control group, but no significant difference was observed between RCs and PGs. Double-labeling analysis of IRF8 with NF-κB and LC3B indicated that IRF8 expression is associated with NF-κB signaling and the autophagy process during periapical lesions. ConclusionsIRF8 could be observed and might possibly be involved in macrophages in the development of periapical lesions.

Differentiation of periapical granulomas and cysts by using dental MRI: a pilot study

The purpose of this pilot study was to evaluate whether periapical granulomas can be differentiated from periapical cysts in vivo by using dental magnetic resonance imaging (MRI). Prior to apicoectomy, 11 patients with radiographically confirmed periapical lesions underwent dental MRI, including fat-saturated T2-weighted (T2wFS) images, non-contrast-enhanced T1-weighted images with and without fat saturation (T1w/T1wFS), and contrast-enhanced fat-saturated T1-weighted (T1wFS+C) images. Two independent observers performed structured image analysis of MRI datasets twice. A total of 15 diagnostic MRI criteria were evaluated, and histopathological results (6 granulomas and 5 cysts) were compared with MRI characteristics. Statistical analysis was performed using intraclass correlation coefficient (ICC), Cohen’s kappa (κ), Mann–Whitney U-test and Fisher’s exact test. Lesion identification and consecutive structured image analysis was possible on T2wFS and T1wFS+C MRI images. A high reproducibility was shown for MRI measurements of the maximum lesion diameter (intraobserver ICC = 0.996/0.998; interobserver ICC = 0.997), for the “peripheral rim” thickness (intraobserver ICC = 0.988/0.984; interobserver ICC = 0.970), and for all non-quantitative MRI criteria (intraobserver-κ = 0.990/0.995; interobserver-κ = 0.988). In accordance with histopathological results, six MRI criteria allowed for a clear differentiation between cysts and granulomas: (1) outer margin of lesion, (2) texture of “peripheral rim” in T1wFS+C, (3) texture of “lesion center” in T2wFS, (4) surrounding tissue involvement in T2wFS, (5) surrounding tissue involvement in T1wFS+C and (6) maximum “peripheral rim” thickness (all: P < 0.05). In conclusion, this pilot study indicates that radiation-free dental MRI enables a reliable differentiation between periapical cysts and granulomas in vivo. Thus, MRI may substantially improve treatment strategies and help to avoid unnecessary surgery in apical periodontitis.

Acme, Pathosis, Furuncle: the Periapical Granuloma

Acme, Pathosis, Furuncle: the Periapical Granuloma

Progress in the diagnosis of florid cemento-osseous dysplasia

Florid cemento-osseous dysplasia (FLCOD) is a rare, extensive bone metabolism disorder, which occurs only in the jaw bone. It is usually asymptomatic for a long time and discovered incidentally during a radiological examination. The characteristics of FLCOD in the initial stages are similar to those of periapical granuloma or jaw cyst, which may lead to misdiagnosis. After the lesion is mature, the imaging findings show that radiopaque with a thin radiolucent peripheral halo, which is crucial for the diagnosis of FLCOD, but other jaw lesions have similar imaging findings. Due to the poor blood supply of the lesion, the alveolar bone of root apices of vital teeth is slow to heal after trauma, increasing the chance of infection, which can lead to the osteomyelitis of the jaws and emerge sequestrum. This paper reviews the aspects of pathogenesis, clinical characteristics, diagnosis, differential diagnosis and treatment.

Apical periodontitis: preliminary assessment of microbiota by 16S rRNA high throughput amplicon target sequencing

BackgroundApical periodontitis includes periapical granulomas and radicular cysts, which are histologically distinguished by the absence and the presence of an epithelial lining, respectively. The main cause of apical periodontitis is the bacterial colonization of the root canal space. This research aimed at assessing whether and how periapical granulomas and radicular cysts differ in terms of microbiota using high throughput amplicon target sequencing (HTS) techniques.MethodsThis study included 5 cases of Periapical Granulomas (PGs) and 5 cases of Radicular Cysts (RCs) selected on the base of histology out of 37 patients from January 2015 to February 2016. Complete medical history, panoramic radiograms (OPTs) and histologic records of each patient were assessed. Only lesions greater than 1 cm in diameter and developed in proximity to teeth with bad prognosis were included. The microbiota present in periapical granulomas and radicular cysts thus retrieved was finely characterized by pyrosequencing of the 16S rRNA genes.ResultsThe core of OTUs shared between periapical granulomas and radicular cysts was dominated by the presence of facultative anaerobes taxa such as: Lactococcus lactis, Propionibacterium acnes, Staphylococcus warneri, Acinetobacter johnsonii and Gemellales. L. lactis, the main OTUs of the entire datasets, was associated with periapical granuloma samples. Consistently with literature, the anaerobic taxa detected were most abundant in radicular cyst samples. Indeed, a higher abundance of presumptive predicted metabolic pathways related to Lipopolysaccharide biosynthesis was found in radicular cyst samples.ConclusionsThe present pilot study confirmed the different microbial characterization of the two main apical periodontitis types and shade light on the possible role of L. lactis in periapical granulomas.

Immunohistochemical Analysis of Galectins-1, -3, and -7 in Periapical Granulomas, Radicular Cysts, and Residual Radicular Cysts

IntroductionGalectins play important roles in immunoinflammatory responses, but their participation in the development of periapical lesions remains unclear. This study aimed to evaluate the expressions of galectins-1, -3, and -7 in periapical lesions, correlating them with the intensity of the inflammatory infiltrate and the pattern of the cystic epithelium. MethodsTwenty periapical granulomas (PGs), 20 radicular cysts (RCs), and 20 residual radicular cysts (RRCs) were submitted to immunohistochemistry using anti–galectin-1, -3, and -7 antibodies. The percentage of immunopositive cells in epithelial and connective tissues was determined. ResultsIn connective tissue, PGs exhibited higher cytoplasmic/membrane expression of galectins-1 and -7 than RCs and RRCs (P < .05). There was higher nuclear expression of galectin-1 in PGs compared with RCs and RRCs (P < .05). The expression of galectins-1 and -7 in connective tissue was higher in lesions with grade III inflammation (P < .05). No significant differences in galectin-3 immunoexpression were observed for any of the parameters evaluated (P > .05). In the epithelial component, a higher nuclear expression of galectin-7 was detected in RRCs (P < .05), and a higher cytoplasmic/membrane expression of this protein was found in cysts with hyperplastic epithelium (P < .05). Positive correlations were observed between the nuclear and cytoplasmic/membrane expression of galectin-1 in connective tissue (P < .05) as well as between the nuclear and cytoplasmic/membrane expression of galectin-7 in epithelial tissue of cysts (P < .05). ConclusionsGalectins-1 and -7 may play important roles in the pathogenesis of PGs, RCs, and RRCs. On the other hand, the present results suggest only a minor involvement of galectin-3 in the development of these lesions.

A potential role for the silent information regulator 2 homologue 1 (SIRT1) in periapical periodontitis.

To investigate the role played by silent information regulator 2 homologue 1 (SIRT1) during angiogenesis of periapical periodontitis. 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. 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. 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.

Comparative evaluation of conventional radiography and color doppler ultrasound imaging in differentiating periapical lesions

Background: Pathological changes in body architecture and disease progression can be detected with radiographs. Accurate diagnosis of this pathological process is necessary for successful treatment and for predictable outcomes. One of the recent advances in achieving this is the advent of diagnostic ultrasonography in identification and differentiating the periapical lesions. Aim of the study is to assess and compare the diagnostic capability of conventional radiography and colour Doppler ultrasound imaging in the identification and differentiating the periapical lesions.Methods: Twenty patients with periapical lesions of pulpal origin which were clinically diagnosed and indicated for extraction were selected for the study. Pre-operative periapical radiographs were obtained. Pre-operative ultrasound examination was performed and the images were assessed for the size, contents, vascular supply and to detect whether the lesion is a periapical abscess, periapical granuloma or periapical cyst. Extraction was performed including curettage of the periapical tissues to enable histopathological investigation, which provides the gold standard diagnosis. The results from the biopsies of the lesions were compared with radiological and ultrasound results and statistically analysed.Result: Of the twenty cases studied, ultrasound could detect 4 periapical abscess, 9 periapical Granuloma and 7 periapical cysts. But histopathologically there were 4 periapical abscess, 7 periapical granulomas and 9 periapical cysts. Two of the periapical cysts were misdiagnosed as periapical Granuloma ultrasonographically. Correlation between ultrasonography and histopathology is 90 percent and between conventional radiography and ultrasonography is 90 percent. Sensitivity of this examination is 88.89 percent.Conclusion: Ultrasound imaging has the potential to be used for the evaluation of periapical lesions of endodontic origin. However, further studies are required to establish a definite correlation.DOI:10.21276/AOHDR.2015

Differential expression of macrophage antigens in periapical lesions: a potential role for macrophage polarization

Background and aim Periapical lesions are considered as the most common lesions that associated with necrotic teeth. Histopathologically, these lesions are accompanied with variable amount of inflammatory cells; among them, macrophages are present in a significant number. This study was planned to assess the role of macrophage subpopulations in the pathogenesis of periapical lesions through the presence of M1 and M2 macrophages. Materials and method Twenty cases of periapical lesions including radicular cysts and periapical granuloma (10 cases each) were selected. Immunohistochemical expressions of CD68, CD163, CD204 and pancytokeratin were evaluated. Results M1 macrophages (CD68+ and CD204+) were strongly associated with periapical granuloma. In radicular cyst, the total number of macrophages was lower than that in periapical granuloma and they were M2 macrophages (CD163+). Conclusion Macrophages contributed to the inflammatory response of periapical lesions. M1 macrophages were associated with periapical granuloma while M2 macrophages were associated with radicular cyst. Transformation of periapical granuloma to radicular cysts requires M2 macrophage polarization.

Expression of the Forkhead box transcription factor Foxo3a in human periapical granulomas.

It has been reported that Forkhead box transcription factor class O3a (Foxo3a) is expressed in rheumatoid arthritis, a chronic inflammatory condition accompanied by bone resorption, and plays a role in its pathology. However, it has remained unclear whether Foxo3a is involved in the pathogenesis of periapical granulomas. The present study was performed to compare the expression of Foxo3a in periapical granulomas and healthy gingival tissues. Samples were obtained surgically from patients, and subjected to hematoxylin-eosin staining for histopathologic diagnosis. Two-color immunofluorescence staining was also performed using antibodies against Foxo3a and markers for three types of inflammatory cells: neutrophils, T lymphocytes, and B lymphocytes. This revealed that Foxo3a was expressed in all three cell types in periapical granulomas but not in healthy gingival tissues. Foxo3a was expressed in 82.1%, 78.3%, and 77.5% of neutrophils, T lymphocytes, and B lymphocytes, respectively, and statistical analysis using the Kruskal-Wallis test followed by the Steel-Dwass test showed no significant difference of Foxo3a expression among the three cell types. Our results suggest that Foxo3a transcription factors may be involved in the pathogenesis of periapical granulomas.

Expression of silent information regulator 2 homolog 1 (SIRT1) in periapical granulomas.

Silent information regulator 2 homolog 1 (SIRT1) inhibits oxidative injury and has anti-inflammatory effects. SIRT1 may be involved in healing of periapical periodontitis; however, SIRT1 expression in periapical periodontitis lesions has not been investigated. This study evaluated SIRT1 expression and a marker of oxidative stress-8-hydroxy-2'-deoxyguanosine (8-OHdG)-in periapical granulomas. First, we used real-time polymerase chain reaction to determine whether U-937 monocytes express SIRT1. U-937 cells treated with the SIRT1 activator resveratrol exhibited the highest SIRT1 mRNA level after 6-h incubation. By contrast, treating cells with the SIRT1 inhibitor sirtinol returned SIRT1 expression level to that of the control. In addition, immunocytochemical analysis using cytospin specimens showed that U-937 cells co-expressed SIRT1 and Ki-67. Dual-color immunofluorescence imaging showed that round cells in periapical granulomas co-expressed SIRT1 and 8-OHdG; however, neither was expressed in healthy gingival tissues. The number of 8-OHdG-expressing cells was significantly greater than the number of SIRT1-expressing cells. Our findings suggest that macrophages express SIRT1 and that wound healing in periapical granulomas is enhanced by a SIRT1-mediated reduction in the level of oxidative stress.