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

Introduction

Galectins 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.

Correlation between clinical and histopathological diagnoses in periapical inflammatory lesions

Aim: The purpose of the present study was to evaluate the correlation between clinical and histopathological diagnoses of periapical inflammatory lesions, focusing mainly on cystic conditions. Methods: Files dating from 1998 to 2006 at the Oral Pathology Laboratory, School of Dentistry, Alfenas Federal University, Brazil, were reviewed to identify cases with histopathological diagnoses of periapical inflammatory lesions. A total of 1788 files were analyzed, and 255 cases were identified with clinical diagnoses of periapical inflammatory lesions. Results: The most prevalent clinical diagnosis was apical periodontal cyst (59%), followed by periapical granuloma (20%), and dentoalveolar abscess (2%). After histopathological analysis, 53% of the cases represented apical periodontal cyst, 42% periapical granuloma, and 5% dentoalveolar abscess. Conclusions: The outcomes of the present study show a high prevalence of periapical cysts among periapical inflammatory lesions. Moreover, this study highlights the importance of histopathological evaluation for the correct diagnosis of periapical inflammatory lesions.     

Apical periodontitis and resoprtion of the root canal wall

Abstract The incidence, extent and distribution of root canal wall resorption were studied in 100 extracted human teeth with chronic periapical lesions. Scanning electron microscopy showed that intracanal dentin resorption had occurred in all teeth. There was no difference between teeth with apical granulomas or radicular cysts. The resorption process was generalized and intensive in the apical third of the root canal, whereas the resorption lacunae were more irregularly spread in the middle and cervical thirds of the canal. Intracanal dentin resorption should be taken into account during endodontic treatment, especially when establishing the apical limit of root canal instrumentation.     

Higher Expression of Galectin-3 and Galectin-9 in Periapical Granulomas than in Radicular Cysts and an Increased Toll-like Receptor-2 and Toll-like Receptor-4 Expression Are Associated with Reactivation of Periapical Inflammation

Introduction

Cysts and periapical granulomas are inflammatory reactions that develop in response to periapical infection by microbial species in dental root canal. It is known that toll-like receptors (TLRs) are pathogen recognition molecules and that galectins are lectins that can be associated with the inflammatory process, stimulating or inhibiting the immune system. The objective of this study was to evaluate the in situ expression of TLRs and galectins in radicular cysts and periapical granulomas.

Methods

We analyzed 62 cases (30 radicular cysts, 27 periapical granulomas, and 5 control cases). Indirect immunohistochemistry was used to evaluate the expression of TLRs (TRL-2 and TLR-4) and galectins (Gal-3 and Gal-9).

Results

The expression of Gal-3 and Gal-9 was significantly higher in periapical granulomas and radicular cysts than in the control group. Similarly, both Gal-3 and Gal-9 were expressed significantly more in periapical granulomas than in radicular cysts. The expression of TLR-2 was significantly higher in periapical granulomas and radicular cysts than in the control group, and it was also significantly higher in radicular cysts with sinus tract than in the cases without sinus tract. Furthermore, the expression of TLR-4 was significantly higher in the cases of periapical granulomas with sinus tract than in the cases without sinus tract.

Conclusions

Gal-3/Gal-9 and TLR-2/TLR-4 expression in the periapical granulomas and radicular cysts is associated with reactive periapical inflammation. Pathobiology of periapical disease is a very complex interplay of many bioactive molecules involved in immunoinflammatory responses. Up-regulation of these bioactive molecules might be an important modulator of inflammatory periapical lesions.     

Repair of Extensive Apical Root Resorption Associated with Apical Periodontitis: Radiographic and Histologic Observations after 25 Years

Introduction

Root resorption is a frequent finding in teeth with apical periodontitis. In cases of severe apical periodontitis, root resorption may involve not only cementum but also dentin. Resorbed tooth structures can only be repaired with cementum because stem cells in the periradicular tissues are not capable of differentiating into odontoblasts. This article reports the repair of extensive apical root resorption associated with apical periodontitis 25 years after treatment.

Methods

A 51-year-old man presented with pulp necrosis and symptomatic apical periodontitis in tooth #7. The periapical radiograph showed a large radiolucent periradicular lesion and severe root resorption. Nonsurgical root canal therapy was performed. Twenty-five years after treatment, a crown fracture developed, and the tooth could not be restored. The periapical radiograph revealed complete healing of the previous apical periodontitis lesion and restoration of the resorbed root structure. The tooth was removed and examined histologically.

Results

The apical canal was almost completely filled with a cementumlike tissue with some strands of entrapped vital uninflamed connective tissue. Areas of cementum and dentin resorption in the apical third were repaired by a combination of cellular and acellular cementum to which periodontal ligament fibers were attached.

Conclusions

Root resorption caused by apical periodontitis can be restored almost to its normal structure after adequate nonsurgical root canal treatment that succeeded in controlling infection. The mechanisms behind this process are not clear but probably involve signaling pathways regulating root development, cell-cell and cell-matrix interaction, and morphogens.     

Immunoexpression of Transforming Growth Factor Beta and Interferon Gamma in Radicular and Dentigerous Cysts

Introduction

The aim of this study was to evaluate and compare the immunohistochemical expression of transforming growing factor beta (TGF-β) and interferon gamma (IFN-γ) between radicular cysts (RCs) and dentigerous cysts (DCs).

Methods

Twenty RCs and DCs were selected for analysis of the immunoexpression of TGF-β and IFN-γ in the epithelium and capsule.

Results

The cell reactivity of TGF-β and IFN-γ in the lining epithelium and capsule of RCs showed no significant differences when compared with DCs (P > .05). There was a tendency of a higher expression of TGF-β in the capsule of DCs.

Conclusions

Our results showed the presence of TGF-β and IFN-γ in RCs and DCs, supporting the hypothesis that both participate in the development of these lesions, where IFN-γ usually plays a role in bone resorption, which is counterbalanced by the osteoprotective activity performed by TGF-β.     

Prevalence of Ciliated Epithelium in Apical Periodontitis Lesions

Introduction

This article reports on the morphologic features and the frequency of ciliated epithelium in apical cysts and discusses its origin.

Methods

The study material consisted of 167 human apical periodontitis lesions obtained consecutively from patients presenting for treatment during a period of 12 years in a dental practice operated by one of the authors. All of the lesions were obtained still attached to the root apices of teeth with untreated (93 lesions) or treated canals (74 lesions). The former were obtained by extraction and the latter by extraction or apical surgery. Specimens were processed for histopathologic and histobacteriologic analyses. Lesions were classified, and the type of epithelium, if present, was recorded.

Results

Of the lesions analyzed, 49 (29%) were diagnosed as cysts. Of these, 26 (53%) were found in untreated teeth, and 23 (47%) related to root canal–treated teeth. Ciliated columnar epithelium was observed partially or completely lining the cyst wall in 4 cysts, and all of them occurred in untreated maxillary molars. Three of these lesions were categorized as pocket cysts, and the other was a true cyst.

Conclusions

Ciliated columnar epithelium-lined cysts corresponded to approximately 2% of the apical periodontitis lesions and 8% of the cysts of endodontic origin in the population studied. This epithelium is highly likely to have a sinus origin in the majority of cases. However, the possibility of prosoplasia or upgraded differentiation into ciliated epithelium from the typical cystic lining squamous epithelium may also be considered.     

Nonendodontic Lesions Misdiagnosed as Apical Periodontitis Lesions: Series of Case Reports and Review of Literature

Introduction

This study aimed to analyze cases referred from a reference service in oral pathology that were initially misdiagnosed as periapical lesions of endodontic origin and to perform a review of the literature regarding lesions located in the apical area of teeth with a nonendodontic source.

Methods

A survey was made of clinical cases derived from the service of oral pathology from 2002 to 2012. The pertinent literature was also reviewed using ScienceDirect and PubMed databases. The lesions were grouped into benign lesions mimicking endodontic periapical lesions (BLMEPLs), malignant lesions mimicking endodontic periapical lesions (MLMEPLs), and Stafne bone cavities. The clinical presentations were divided into lesions with swelling without pain, lesions with swelling and pain, and lesions without swelling but presenting with pain.

Results

The results showed that 66% (37/56) of cases represented benign lesions, 29% (16/56) malignant lesions, and 5% (3/56) Stafne bone cavities. The most commonly reported BLMEPLs were ameloblastomas (21%) followed by nasopalatine duct cysts (13.5%). The most frequently cited MLMEPLs were metastatic injuries (31.5%) followed by carcinomas (25%). The main clinical presentation of BLMEPLs was pain, whereas that of MLMEPLs was swelling associated with pain; Stafne bone cavities displayed particular clinical findings.

Conclusions

Clinical and radiologic aspects as well as the analysis of the patients' medical history, pulp vitality tests, and aspiration are essential tools for developing a correct diagnosis of periapical lesions of endodontic origin. However, if the instruments mentioned earlier indicate a lesion of nonendodontic origin, a biopsy and subsequent histopathological analysis are mandatory.     

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

Introduction

The 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.

人慢性根尖周炎中白细胞介素17F的定位表达研究

目的 初步探讨白细胞介素( interleukin,IL) 17F在人根尖周炎病损组织中的表达情况,以期为根尖周炎的发病机制研究提供依据.方法 收集安徽医科大学口腔医学院口腔颌面外科2009年11月至2011年8月经根尖手术切除的根尖周炎病损组织并做病理鉴定.经过组织切片、HE染色和显微镜病理观察,共有根尖囊肿33例,根尖肉芽肿18例.将这些组织作为试验组用于免疫组织化学分析IL-17F的表达情况,用磷酸盐缓冲液代替一抗作阴性对照,根尖囊肿和根尖肉芽肿阴性对照组各5例.收集埋伏阻生智齿拔除时需凿骨患者的健康牙槽骨质5例,作为正常对照组.对根尖囊肿和根尖肉芽肿中IL-17F的蛋白平均吸光度值(A值)进行方差齐性检验,若方差齐则行t检验,若方差不齐则行秩和检验,检验水准为α =0.05.结果 IL-17F在两组慢性根尖周炎组织中的上皮细胞、淋巴样细胞、成纤维细胞和内皮细胞中均有表达;正常对照组和阴性对照组未见IL-17F的表达.根尖囊肿中IL-17F的蛋白平均积分吸光度值(A值)为0.8852±0.0576,根尖肉芽肿为0.2365±0.0708,二者差异有统计学意义(Z=3.735,P＜0.01).结论 IL-17F存在于人根尖周炎病损组织中;IL-17F可能参与了人根尖周炎疾病的发病进程,且IL-17F在根尖囊肿和根尖肉芽肿中的表达强度具有差异性.     

C1 Silencing Attenuates Inflammation and Alveolar Bone Resorption in Endodontic Disease

IntroductionEndodontic disease, 1 of the most prevalent chronic infectious diseases worldwide, occurs when the dental pulp becomes infected and inflamed, leading to bone destruction around the tooth root, severe pain, and tooth loss. Although many studies have tried to develop therapies to alleviate the bone erosion and inflammation associated with endodontic disease, there is an urgent need for an effective treatment.MethodsIn this study, we used a gene-based therapy approach by administering recombinant adeno-associated virus (AAV)-mediated Atp6v1c1 knockdown to target both periapical bone resorption and inflammation in the mouse model of endodontic disease.ResultsThe results showed that Atp6v1c1 knockdown is simultaneously capable of reducing bone resorption by 70% through impaired osteoclast activation, inhibiting inflammation by decreasing T-cell infiltration in the periapical lesion by 75%, and protecting the periodontal ligament from destruction caused by inflammation. Notably, AAV-mediated gene therapy of Atp6v1c1 knockdown significantly reduced proinflammatory cytokine expression, including tumor necrosis factor α, interleukin 1α, interleukin 17, interleukin 12, and interleukin 6 levels in periapical tissues caused by bacterial infection. Quantitative real-time polymerase chain reaction revealed that Atp6v1c1 knockdown reduced osteoclast-specific functional genes (ie, Ctsk) in periapical tissues.ConclusionsOur results showed that AAV-mediated Atp6v1c1 knockdown in periapical tissues slowed endodontic disease progression, prevented bone erosion, and alleviated inflammation in the periapical tissues and periodontal ligament potentially through regulation of toll-like receptor signaling, indicating that targeting Atp6v1c1 may facilitate the design of novel therapeutic approaches to reduce inflammation and bone erosion in endodontic disease.     

基质金属蛋白酶诱导因子和亲环素A在人根尖囊肿和根尖肉芽肿中的表达及临床意义

目的: 检测细胞外基质金属蛋白酶诱导因子(CD147)和亲环素A(CypA)在根尖肉芽肿和根尖囊肿中的表达,探讨CD147和CyPA在人慢性根尖周炎发生发展中的作用。方法: 收集经根尖手术切除所获得的根尖肉芽肿35例和根尖囊肿30例作为实验组,同时收集埋伏阻生智齿拔除术或行牙槽骨修整术凿下的8例健康牙槽骨作为正常对照组。CBCT图像记录病例的病损大小。运用免疫组织化学法检测所有样本中CD147和CypA的蛋白表达,分析CD147和CypA的蛋白表达水平。结果: 根尖囊肿组两种蛋白的表达水平均高于肉芽肿组(P<0.05)。CD147和CypA 的蛋白表达水平在根尖囊肿和根尖肉芽肿中呈正相关(P<0.05);CD147和CypA 的表达水平均与慢性根尖周炎的病变大小呈正相关(P<0.05)。结论: CD147和CypA可能参与根尖周病损的炎性反应和骨质吸收。CD147-CypA相互作用在人慢性根尖周病的发生发展过程中可能发挥了某种协同作用。     

Prevalence of Nonendodontic Diagnoses in Periapical Biopsies: A 6-year Institutional Experience

IntroductionThe purpose of this study was to identify nonendodontic periapical lesions (NPLs) mimicking endodontic pathosis, which are most frequently encountered by clinicians.MethodsA retrospective study was conducted on biopsies obtained from 2015–2020 at Texas A&M College of Dentistry’s oral pathology laboratory. The online database was screened for cases submitted as suspected endodontic pathology using specific key words. Histologic diagnoses were collected to determine the prevalence of NPLs that were originally thought to be of endodontic origin. The frequency and percentage of endodontic pathology and NPLs were documented.ResultsAmong 6704 biopsies clinically diagnosed as endodontic lesions, 190 (2.8%) were histopathologically diagnosed as NPLs. The most frequent NPLs were odontogenic keratocytes’ (n = 70, 36.8%), cemento-osseous dysplasia (n = 27, 14.2%), and dentigerous cysts (n = 22, 11.6%). Of all NPLs, 3.7% were malignant neoplasms, with the most common diagnosis being squamous cell carcinoma. Of 6514 endodontic histologic diagnoses, the prevalence of periapical granulomas and cysts was 60.2% (n = 3924) and 39.1% (n = 2549), respectively.ConclusionsAlthough most endodontic submissions are likely to be histologically diagnosed as periapical granulomas or cysts, the clinician should be aware that a small portion of these lesions may be nonendodontic in origin and possibly neoplastic in nature. Histopathologic evaluation of biopsied specimens is critical to achieve a proper diagnosis to ensure the appropriate management of patients.     

Immunoexpression of Interleukin 17 in Apical Periodontitis Lesions

Introduction

Interleukin (IL)-17 expression has been detected in apical periodontitis lesions, but its role in the disease process remains unclear. The present study compared the expression of IL-17 in periradicular cysts and granulomas and evaluated the association of this cytokine with clinical and radiographic findings.

Methods

Apical periodontitis lesions (18 cysts and 20 granulomas) were obtained from 38 patients subjected to periradicular surgery. Some clinical, radiographic, and cone-beam computed tomographic features were recorded. Silanized slides containing paraffin sections were used for the immunohistochemical reactions using anti–IL-17 antibody. Image analysis was performed using an optical microscope, and each sample was divided into 5 high-power fields, which were evaluated for the expression of IL-17 in the epithelium and connective tissues. Results were evaluated for correlations with the lesion size and the occurrence of symptoms and sinus tract.

Results

Expression of IL-17 was significantly higher in cysts than in granulomas (P = .02). Among the periradicular cysts, a thin epithelium showed significantly increased labeling for IL-17 when compared with a hyperplastic epithelium (P = .003). IL-17 expression was usually associated with focal accumulations of polymorphonuclear leukocytes. No association of IL-17 expression with symptoms, sinus tract, or lesion size was observed (P > .05).

Conclusions

The present study reinforces the notion that IL-17 may take part in the pathogenesis of apical periodontitis lesions. A role in the exacerbation of chronic inflammation and cyst formation is suspected. Further studies are required to shed light on the specific functions of IL-17 in periradicular inflammatory processes.     

Evaluation of the Reliability and Accuracy of Using Cone-beam Computed Tomography for Diagnosing Periapical Cysts from Granulomas

Introduction

The purpose of this study was to evaluate the reliability and accuracy of cone-beam computed tomographic (CBCT) imaging against the histopathologic diagnosis for the differential diagnosis of periapical cysts (cavitated lesions) from (solid) granulomas.

Methods

Thirty-six periapical lesions were imaged using CBCT scans. Apicoectomy surgeries were conducted for histopathological examination. Evaluator 1 examined each CBCT scan for the presence of 6 radiologic characteristics of a cyst (ie, location, periphery, shape, internal structure, effects on surrounding structure, and perforation of the cortical plate). Not every cyst showed all radiologic features (eg, not all cysts perforate the cortical plate). For the purpose of finding the minimum number of diagnostic criteria present in a scan to diagnose a lesion as a cyst, we conducted 6 receiver operating characteristic curve analyses comparing CBCT diagnoses with the histopathologic diagnosis. Two other independent evaluators examined the CBCT lesions. Statistical tests were conducted to examine the accuracy, inter-rater reliability, and intrarater reliability of CBCT images.

Results

Findings showed that a score of ≥4 positive findings was the optimal scoring system. The accuracies of differential diagnoses of 3 evaluators were moderate (area under the curve = 0.76, 0.70, and 0.69 for evaluators 1, 2, and 3, respectively). The inter-rater agreement of the 3 evaluators was excellent (α = 0.87). The intrarater agreement was good to excellent (κ = 0.71, 0.76, and 0.77).

Conclusions

CBCT images can provide a moderately accurate diagnosis between cysts and granulomas.     

Preservation and demonstration of mast cells in human apical granulomas and radicular cysts

abstract – The investigation concerns the preservation and demonstration of human mast cells in undemineralized material. The material comprised human apical granulomas and radicular cysts dissected from extracted teeth or obtained by apicoectomy and cyst removal. Chronically inflamed human gingiva, rat tongue, and rat peritoneum served as control tissues. The following fixations were tested: 4% formaldehyde solution buffered to pH 7.2, Newcomer's fluid, and a 4% aqueous solution of basic lead acetate with formalin 1:10 added. The following dyes and fluorochromes were tested: toluidine blue in various concentrations and at various pH values, Astra-blue, the esterase substrate naphthol-AS-D-chloroacetate in combination with GBC, acridine orange in various concentrations and at various pH values, berberine-sulfate, and thioflavin T. Abundant mast cells were demonstrated in all granulomas and cysts with at least one of the staining methods tested. A 4% lead acetate solution with formalin added proved the best fixative for the preservation of the human mast cells, whereas staining with Astra-blue appeared the superior technique for demonstrating the human mast cells. Acridine orange showed the best secondary fluorescence of the fluorochromes tested. The best results with this dye were obtained using a 0.03% solution in 5% AlSO₄.     

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

Introduction

The 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.

Overlapping Protective and Destructive Regulatory Pathways in Apical Periodontitis

Introduction

Protective and destructive immunoreactions take place simultaneously in apical periodontitis. However, the same reactions defending the periapical area from infection-derived damage may also result in host tissue injury.

Methods

The inflammatory reaction of the periapical tissues is self-limited. Regeneration of the injured tooth-supporting structures may follow elimination of the causative microbial irritation.

Results

Recent experimental and clinical observations have identified important interplay between positive and negative regulatory pathways. A network of stimulatory and inhibitory feedback loops may influence the intensity of the defense and inflammatory responses and the balance between bone resorption and regeneration, resulting in lesion expansion or healing of apical periodontitis.

Conclusions

We critically discuss research data on regulatory mechanisms that control the activity of host effector cells and signaling molecules during interactions with pathogenic microbes.     

Absence of Tumor Necrosis Factor Receptor 1 Inhibits Osteoclast Activity in Apical Dental Resorption Caused by Endodontic Infection in Mice

IntroductionThe aim of this study was to evaluate osteoclastogenesis and dental resorption resulting from endodontic infection in wild-type (WT) and tumor necrosis factor receptor 1 genetically deficient (TNFR1 KO) mice.MethodsAfter approval by the ethics committee on the use of animals, 40 mice were distributed into 2 experimental groups based on time periods: 14 days (n = 10 WT mice and n = 10 TNFR1 KO mice) and 42 days (n = 10 WT mice and n = 10 TNFR1 KO mice). After these periods, morphometric analysis was performed using bright field and fluorescence microscopy and tartrate-resistant acid phosphatase histoenzymology to identify osteoclasts. One-way analysis of variance followed by the Tukey post hoc test was used for the statistical analysis (α = 0.05).ResultsWT mice in the 42-day period had a greater apical dental resorption in the distal root of the first molar than TNFR1 KO mice (P < .05). On the other hand, TNFR1 KO mice showed a smaller number of osteoclasts on the dental surface than WT mice (P < .05).ConclusionsWT mice with apical periodontitis had more extensive apical dental resorptions and a larger number of osteoclasts on the tooth surface than TNFR1 KO mice.