Comparative Metabolomics Reveals the Microenvironment of Common T-Helper Cells and Differential Immune Cells Linked to Unique Periapical Lesions.

Periapical abscesses, radicular cysts, and periapical granulomas are the most frequently identified pathological lesions in the alveolar bone. While little is known about the initiation and progression of these conditions, the metabolic environment and the related immunological behaviors were examined for the first time to model the development of each pathological condition. Metabolites were extracted from each lesion and profiled using gas chromatography-mass spectrometry in comparison with healthy pulp tissue. The metabolites were clustered and linked to their related immune cell fractions. Clusters I and J in the periapical abscess upregulated the expression of MMP-9, IL-8, CYP4F3, and VEGF, while clusters L and M were related to lipophagy and apoptosis in radicular cyst, and cluster P in periapical granuloma, which contains L-(+)-lactic acid and ethylene glycol, was related to granuloma formation. Oleic acid, 17-octadecynoic acid, 1-nonadecene, and L-(+)-lactic acid were significantly the highest unique metabolites in healthy pulp tissue, periapical abscess, radicular cyst, and periapical granuloma, respectively. The correlated enriched metabolic pathways were identified, and the related active genes were predicted. Glutamatergic synapse (16-20),-hydroxyeicosatetraenoic acids, lipophagy, and retinoid X receptor coupled with vitamin D receptor were the most significantly enriched pathways in healthy control, abscess, cyst, and granuloma, respectively. Compared with the healthy control, significant upregulation in the gene expression of CYP4F3, VEGF, IL-8, TLR2 (P < 0.0001), and MMP-9 (P < 0.001) was found in the abscesses. While IL-12A was significantly upregulated in cysts (P < 0.01), IL-17A represents the highest significantly upregulated gene in granulomas (P < 0.0001). From the predicted active genes, CIBERSORT suggested the presence of natural killer cells, dendritic cells, pro-inflammatory M1 macrophages, and anti-inflammatory M2 macrophages in different proportions. In addition, the single nucleotide polymorphisms related to IL-10, IL-12A, and IL-17D genes were shown to be associated with periapical lesions and other oral lesions. Collectively, the unique metabolism and related immune response shape up an environment that initiates and maintains the existence and progression of these oral lesions, suggesting an important role in diagnosis and effective targeted therapy.

Salivary Metabolomics Fingerprint of Chronic Apical Abscess with Sinus Tract: A Pilot Study.

Chronic apical abscess (CAA) is a lesion of apical periodontitis mostly characterized by areas of liquefactive necrosis with disintegrating polymorphonuclear neutrophils surrounded by macrophages. Its presence leads to local bacterial infection, systemic inflammatory response, pain, and swelling. The use of a novel approach for the study of CAA, such as metabolomics, seems to be important since it has proved to be a powerful tool for biomarkers discovery which could give novel molecular insight on CAA. So, the aim of this study was to verify the possibility to identify the metabolic fingerprint of CAA through the analysis of saliva samples. Nineteen patients were selected for this study: eleven patients affected by CAA with a sinus tract constituted the study group whereas eight patients without clinical and radiographic signs of CAA formed the healthy control group. Saliva samples were collected from each subject and immediately frozen at -80°C. Metabolomic profiles were obtained using a gas chromatography/mass spectrometry instrument. Subsequently, in order to compare the two groups, a multivariate statistical model was built that resulted to be statistically significant. The class of metabolites characterizing the CAA patients was closely related to the bacterial catabolism, tissue necrosis, and presence of a sinus tract. These preliminary results, for the first time, indicate that saliva samples analyzed by means of GC/MS metabolomics may be useful for identifying the presence of CAA, leading to new insights into this disease.

Development and evaluation of calcium hydroxide-coated, pericardium-based biomembranes for direct pulp capping.

AIM: The aim of the present study was to develop a bovine pericardium biomembrane (BPB) and to evaluate pulp response in vivo. METHODS: A double-layer bovine BPB/chitosan was manufactured, and the porous chitosan side was coated with calcium hydroxide. The microstructure of the matrices was evaluated with electron microscopy. To test pulp response, cavities were prepared on the occlusal surface of Wistar rats' mandibular left first molars and capped with matrices, followed by appropriate adhesives/composite restorations. The animals were divided into three groups: group 1, calcium hydroxide alone; group 2, BPB without calcium hydroxide; and group 3, BPB coated with calcium hydroxide. Specimens were processed and histologically evaluated at 7, 14, and 30 days, postoperatively. RESULTS: Electron microscopy showed porous chitosan surface and a cohesive calcium hydroxide layer. Histological analysis showed that groups 1 and 3 had mild odontoblast layer disorganization, but normal pulp tissue appearance at 7, 14, and 30 days. At the same time points, group 2 showed a loss of general pulp tissue, pulp necrosis, and periapical abscess in some teeth. CONCLUSION: Coated bovine pericardium-based biomembranes resulted in favorable outcomes in cases of pulp exposure after a 30-day observation period, and might protect against injuries caused by adhesive systems and composites.

Cone-beam computed tomographic and histological investigation of regenerative endodontic procedure in an immature mandibular second premolar with chronic apical abscess.

AIM: The aim of the present study was to investigate the tissue generated after regenerative endodontic procedure (REP) in the root canal space of an immature mandibular second premolar with pulp necrosis and chronic apical abscess using cone-beam computed tomographic (CBCT) and histological methods. METHODS: REP was performed in an immature mandibular second premolar. At the 3-year follow up, CBCT scans were taken to evaluate the outcome of treatment. As the tooth was not restorable to function, it was extracted and processed for histological examination. RESULTS: CBCT showed a reduction in size of the periradicular radiolucency, with a marginal increase in root length. Apical closure and thickening of the root canal walls were apparent. Histologically, the root canal space was filled with minimally-inflamed fibrous connective tissue. Some cementum-like mineralized connective tissue was evident on the internal canal walls. The apical third showed cementum-like deposits at the apex and the outer canal walls, without dentin formation. CONCLUSIONS: The present study of a structurally-failed tooth with prior REP demonstrates that the tissue formed within the root canal space was fibrous connective tissue with cementum-like deposition in the canal space. No evidence of dentin- or pulp-like tissue was found.

Histobacteriologic Conditions of the Apical Root Canal System and Periapical Tissues in Teeth Associated with Sinus Tracts.

INTRODUCTION: This histobacteriologic study described the pattern of intraradicular and extraradicular infections in teeth with sinus tracts and chronic apical abscesses. METHODS: The material comprised biopsy specimens from 24 (8 untreated and 16 treated) roots of teeth associated with apical periodontitis and a sinus tract. Specimens were obtained by periradicular surgery or extraction and were processed for histobacteriologic and histopathologic methods. RESULTS: Bacteria were found in the apical root canal system of all specimens, in the main root canal (22 teeth) and within ramifications (17 teeth). Four cases showed no extraradicular infection. Extraradicular bacteria occurred as a biofilm attached to the outer root surface in 17 teeth (5 untreated and 12 treated teeth), as actinomycotic colonies in 2 lesions, and as planktonic cells in 2 lesions. Extraradicular calculus formation (mineralized biofilm) was evident in 10 teeth. CONCLUSIONS: Teeth with chronic apical abscesses and sinus tracts showed a very complex infectious pattern in the apical root canal system and periapical lesion, with a predominance of biofilms.

Chondroblastic osteosarcoma mimicking periapical abscess.

CASE REPORT: The present report describes a case of chondroblastic osteosarcoma in the periapical region of teeth #29, #30, and #31 of an 18-year-old male. Clinical history showed self-reported discomfort in the right posterior gingiva for over a month. Physical examination showed a small expansion and redness of the right mandibular buccal and lingual cortical plates, but no signs of pain or inflammation were observed. All the teeth responded positively to pulp sensibility. Periapical and panoramic radiographs showed slight periapical radiolucency in the roots of teeth #29 and #30, clear periodontal ligament space widening, and evident loss of lamina dura. Incisional biopsy was performed, and based on microscopic findings the diagnosis of chondroblastic osteosarcoma was confirmed. CONCLUSIONS: Non-endodontic diseases associated with tooth root apex, such as chondroblastic osteosarcoma, should be included in differential diagnosis of jaw lesions that resemble periapical abscess.

Chondroblastic osteosarcoma mimicking periapical abscess

Abstract Lesions of non-endodontic origin may mimic periapical abscess. Osteosarcoma is a rare malignant lesion. Case report The present report describes a case of chondroblastic osteosarcoma in the periapical region of teeth #29, #30, and #31 of an 18-year-old male. Clinical history showed self-reported discomfort in the right posterior gingiva for over a month. Physical examination showed a small expansion and redness of the right mandibular buccal and lingual cortical plates, but no signs of pain or inflammation were observed. All the teeth responded positively to pulp sensibility. Periapical and panoramic radiographs showed slight periapical radiolucency in the roots of teeth #29 and #30, clear periodontal ligament space widening, and evident loss of lamina dura. Incisional biopsy was performed, and based on microscopic findings the diagnosis of chondroblastic osteosarcoma was confirmed. Conclusions Non-endodontic diseases associated with tooth root apex, such as chondroblastic osteosarcoma, should be included in differential diagnosis of jaw lesions that resemble periapical abscess.

Evaluación de Lesiones Periapicales en Pacientes Derivados a Cirugía Periapical Mediante Tomografía Computarizada de Haz Cónico / Evaluation of Periapical Lesions by Cone Beam Computed Tomography in Patients Referred for Apical Surgery

El uso de la tomografía computarizada de haz cónico (CBCT) en endodoncia ha ido en aumento, justificando su uso en casos más complejos, como cirugías periapicales. El objetivo fue evaluar las características imagenológicas encontradas en un grupo de pacientes derivados a cirugía periapical, mediante el uso de CBCT. Se realizó un estudio observacional descriptivo, en un grupo de pacientes, derivados a cirugía periapical, a los cuales se realizó un examen de CBCT, evaluación clínica y radiografía periapical. Un total de 18 pacientes fueron examinados (6 hombres y 12 mujeres), cuyas edades estaban entre los 19 y 64 años de edad. El diámetro mayor de las lesiones varió entre 6 mm a 16 mm. El uso de CBCT en cirugías periapicales entrega información más completa al cirujano, ya que permite mayor precisión al realizar el acceso quirúrgico y detecta un mayor número de lesiones periapicales que con la radiografía periapical, logrando en casos complejos un mejor diagnóstico y planificación del tratamiento.

The use of cone beam computed tomography (CBCT) in endodontics has increased, justifying its use in more complex cases, such as apical surgery. The aim was to evaluate the radiologic characteristics found in a group of patients referred to apical surgery, using CBCT. A descriptive study was conducted in a group of patients referred for apical surgery. In these patients, a clinical examination, a conventional radiographic evaluation and CBCT were performed. A total of 18 patients were examined (6 men and 12 women), ages were between 19 and 64 years old. The major diameter of the lesions ranged from 6 mm to 16 mm. The use of CBCT in apical surgery provides more complete information to the surgeon, allowing greater precision when performing surgical access and detects a greater number of periapical lesions than with conventional radiography. In complex cases is possible obtain better diagnosis and treatment planning.

Analysis of Interleukin 17A in periapical abscess and granuloma lesions.

Interleukin 17A (IL-17A) is a proinflammatory cytokine responsible for the initiation and propagation of inflammation. One of its actions is the recruitment of neutrophils to the site of infection. The aim of this study was to investigate whether there is association between IL-17A expression and neutrophil infiltration in periapical abscesses and periapical granulomas, as well as to find which type of T lymphocyte effector (CD4+ or CD8+) expresses IL-17A in these lesions. Elastase, CD4, CD8, and IL-17A were analyzed by immunohistochemistry and immunofluorescence, in the biopsies of periapical lesions. Abscess lesions exhibited the highest labeling area for IL-17A (p = 0.011). During double immunofluorescence staining, there were significantly more CD4+/IL-17A+ cells compared to CD8+/IL-17A+ cells, both in the abscesses (p = 0.025) and granulomas (p = 0.011). In conclusion, IL-17A was intensively expressed in periapical abscesses rich in neutrophils. The high percentage of IL-17A in these cases suggests the participation of this cytokine particularly in the acute stages of the inflammatory process of the periapical lesions.

The root of the problem: Occurrence of typical and atypical periapical pathoses.

BACKGROUND: A preponderance of periapical radiolucencies are of inflammatory etiology (radicular cysts or periapical granulomas) secondary to pulpal disease. In some instances, however, a suspected periapical inflammatory lesion is not a consequence of pulpal disease but instead represents a lesion of noninflammatory origin. The differential diagnosis for such lesions is broad, ranging from odontogenic cysts and tumors to metastatic disease. As the biological behavior of such lesions is varied, the distinction between inflammatory odontogenic periapical lesions and lesions of noninflammatory origin in a periapical location is critical. METHODS: A retrospective study of 5,993 archival periapical biopsies over a span of 15 years from the database of the Oral Pathology Biopsy Service in the Henry M. Goldman School of Dental Medicine at Boston University recorded the incidence of various lesions in a periapical location. RESULTS: Of the cases studied, 97.2% represented lesions of inflammatory origin with histopathologic diagnoses as follows: periapical granuloma (60.0%), radicular cyst (36.7%), periapical fibrous scar (0.27 %), and periapical abscess (0.23 %). The remaining 2.8% cases were lesions of noninflammatory origin with histopathologic diagnoses of odontogenic keratocyst (also known as keratocystic odontogenic tumor), benign fibro-osseous lesions, and ameloblastoma. One patient had Langerhans cell disease, and 1 had central giant cell granuloma. CONCLUSIONS: Although most periapical specimens biopsied represented expected inflammatory periapical lesions, the biological behavior of underdiagnosed lesions may have considerable consequences for both the patient and the clinician. PRACTICAL IMPLICATIONS: This article serves to inform clinicians regarding the diversity of lesions arising in the periapical region of the jaws, to assist in the formulation of differential diagnoses, and to highlight the importance of submission of lesional tissue for histopathologic evaluation and definitive diagnosis when biopsy is clinically indicated.

Complex Apical Intraradicular Infection and Extraradicular Mineralized Biofilms as the Cause of Wet Canals and Treatment Failure: Report of 2 Cases.

This article describes 2 cases that showed persistent intracanal exudation (wet canal) even after several visits of antimicrobial endodontic treatment. Histologic and histobacteriologic investigation was conducted for determination of the cause. The 2 cases involved teeth with apical periodontitis lesions, which presented persistent exudation refractory to treatment after several visits. In case 1, it was not possible to achieve a dry canal, and surgery had to be performed. In case 2, attempts to dry the canal succeeded and the canal was filled, but follow-up examination showed an enlarged apical periodontitis lesion and extraction was performed. Biopsy specimens consisting of the root apex and apical periodontitis lesion for case 1 and the whole root for case 2 were subjected to histologic and histobacteriologic analyses. Both cases showed complex bacterial infection in the apical root, affecting both the intraradicular space and the outer root surface. Case 1 showed bacterial biofilms in ramifications, on untouched walls, and extending to the external root surface to form a thick and partially mineralized structure with high bacterial density. Different bacterial morphotypes were evidenced. Case 2 had a ledge on the apical canal wall created during instrumentation, which was filled with necrotic debris, filling material, and bacteria. The walls of the apical portion of the canal were covered by a bacterial biofilm, which was continuous with a thick extraradicular biofilm covering the cementum and dentin in resorptive defects. The extraradicular biofilm showed areas of mineralization and was dominated by filamentous bacteria. The 2 cases with wet canals and treatment failure were associated with complex persistent infection in the apical part of the root canal system extending to form thick and partially mineralized biofilm structures (calculus) on the outer apical root surface.

Radiographic and histological evaluation of persistent periapical lesions associated with endodontic failures after apical microsurgery.

AIM: To determine the histology of persistent periapical lesions associated with nonsurgical endodontic treatment failures and to compare radiographically the sizes of periapical lesions and the presence or absence of the radiopaque lamina with the histological findings. METHODOLOGY: Ninety-three anterior teeth designated for apical microsurgery were included in the study. After taking standard radiographs of all cases using the parallel technique, the films were scanned and evaluated for the size of periapical radiolucent lesions and the presence or absence of radiopaque lamina by two calibrated observers. Biopsy specimens were obtained during apical microsurgery and examined under light microscopy by oral pathologists. Histological analysis established diagnoses of granuloma, cyst, abscess and scar tissue. Interobserver agreement was evaluated by the kappa test, and the relationship between histological diagnosis and lesion size was analysed by the Pearson's chi-square test. RESULTS: The 93 specimens consisted of 72% periradicular granulomas; 21.5% radicular cysts, including two keratocysts; 4.3% abscesses; and 2.2% scar tissue. Cystic prevalence increased as the size of the periapical lesion increased; however, there was no correlation between the presence of a radiopaque lamina and histological diagnosis of cyst. CONCLUSIONS: Neither radiographic size nor presence of an associated radiopaque line alone was sufficient to determine the type of lesion. Histological examination is required in order to reach to a definitive diagnosis.

Analysis of Interleukin 17A in periapical abscess and granuloma lesions

Abstract Interleukin 17A (IL-17A) is a proinflammatory cytokine responsible for the initiation and propagation of inflammation. One of its actions is the recruitment of neutrophils to the site of infection. The aim of this study was to investigate whether there is association between IL-17A expression and neutrophil infiltration in periapical abscesses and periapical granulomas, as well as to find which type of T lymphocyte effector (CD4+ or CD8+) expresses IL-17A in these lesions. Elastase, CD4, CD8, and IL-17A were analyzed by immunohistochemistry and immunofluorescence, in the biopsies of periapical lesions. Abscess lesions exhibited the highest labeling area for IL-17A (p = 0.011). During double immunofluorescence staining, there were significantly more CD4+/IL-17A+ cells compared to CD8+/IL-17A+ cells, both in the abscesses (p = 0.025) and granulomas (p = 0.011). In conclusion, IL-17A was intensively expressed in periapical abscesses rich in neutrophils. The high percentage of IL-17A in these cases suggests the participation of this cytokine particularly in the acute stages of the inflammatory process of the periapical lesions.

FOXP3 DNA methylation levels as a potential biomarker in the development of periapical lesions.

INTRODUCTION: Epigenetic mechanisms, such as DNA methylation, can modify gene expression patterns without changing the DNA sequence, comprising a tool that cells use to lock genes in the "off" position. Variations in the methylation profile have been correlated to a variety of human diseases. Here, we hypothesize that DNA methylation in immune response-related genes may contribute to the development of periapical lesions. METHODS: The DNA methylation patterns of 22 immune response-related gene promoters were evaluated in 137 human periapical granulomas, 8 apical cysts, and 31 healthy gingival tissues from 2 independent cohorts using a pathway-specific real-time polymerase chain reaction array (EpiTect Methyl II; Qiagen Inc, Valencia, CA). Messenger RNA expression analysis by qualitative polymerase chain reaction was also performed. SABiosciences's hierarchical clustering and methylation (Qiagen, Valencia, CA) and Prism6 software (GraphPad Software, Inc, La Jolla, CA) were used for data analysis. RESULTS: FOXP3 gene promoter showed the highest level of methylation in both periapical granulomas and apical cysts (P < .001), and methylation levels were inversely correlated with FOXP3 messenger RNA expression in the lesions. Furthermore, FOXP3 expression was prevalent in inactive lesions and was positively correlated with interleukin-10 and transforming growth factor beta levels. CONCLUSIONS: Our results suggest that FOXP3 acts as a master switch governing the development and function of T-regulatory cells, whose functions include the inhibition of immune responses and temper inflammation. The observed differential methylation patterns of FOXP3 in periapical lesions may be crucial in determining its suppressive activity and may be involved in periapical lesion development.

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.

Orthodontic movement of endodontically treated teeth.

Often there is the need of moving teeth endodontically treated or teeth still in endodontic treatment. In order to collaborate with the comprehension and substantiation of the following subjects we will discuss: 1) Orthodontic movement in endodontically treated teeth without periapical lesion, 2) Orthodontic movement in endodontically treated teeth with inflammatory periapical lesion, and 3) Orthodontic movement in teeth endodontically treated due to aseptic pulp necrosis by dental trauma. In practically all situations, endodontically treated teeth to be orthodontically moved must be subjected to a careful evaluation by the endodontist about the conditions, adequate or not, of the endodontic treatment. Then, in this paper it was sought to induce an insight for new clinical researches about the theme that may definitely prove the information obtained by interrelations of information in parallel to clinical practice.

Orthodontic movement of endodontically treated teeth

Often there is the need of moving teeth endodontically treated or teeth still in endodontic treatment. In order to collaborate with the comprehension and substantiation of the following subjects will be discussed: 1) Orthodontic movement in endodontically treated teeth without periapical lesion, 2) Orthodontic movement in endodontically treated teeth with inflammatory periapical lesion, and 3) Orthodontic movement in teeth endodontically treated due to aseptic pulp necrosis by dental trauma. In practically all situations, endodontically treated teeth to be orthodontically moved must be subjected to a careful evaluation by the endodontist about the conditions, adequate or not, of the endodontic treatment. Then, in this paper it was sought to induce an insight for new clinical researches about the theme that may definitely prove the information obtained by interrelations of information in parallel to clinical practice.

Com frequência, há a necessidade de movimentar-se dentes endodonticamente tratados ou ainda em tratamento endodôntico. Para colaborar com a compreensão e fundamentação do assunto, abordaremos: 1) a movimentação ortodôntica em dentes endodonticamente tratados sem lesão periapical; 2) a movimentação ortodôntica em dentes endodonticamente tratados com lesão periapical inflamatória; e 3) a movimentação ortodôntica em dentes endodonticamente tratados de necrose pulpar asséptica por traumatismo dentário. Em praticamente todas as situações, dentes endodonticamente tratados a serem movimentados ortodonticamente devem ser submetidos a uma avaliação criteriosa, por parte do endodontista, sobre as condições adequadas ou não do tratamento endodôntico. Em seguida, no presente trabalho procurou-se, singelamente, induzir um insight para novas pesquisas clínicas sobre o tema, que possam definitivamente comprovar os conhecimentos obtidos pela inter-relação de conhecimentos em paralelo à prática clínica.

Clinical, radiographic, and histological observation of a human immature permanent tooth with chronic apical abscess after revitalization treatment.

INTRODUCTION: Revitalization procedures have been widely used for the treatment of immature permanent teeth with apical periodontitis. The treatment procedures appear to be capable of encouraging continued root development and thickening of the canal walls. The nature of tissues formed in the canal space and at the root apex after revitalization has been shown histologically in several animal studies; similar studies in humans were recently reported. METHODS: A 9-year-old boy had a traumatic injury to his upper anterior teeth. Tooth #9 suffered a complicated crown fracture with a pulp exposure, which was restored with a composite resin. The tooth developed a chronic apical abscess. Revitalization procedures were performed on tooth #9 because it was an immature permanent tooth with an open apex and thin canal walls. Twenty-six months after revitalization, the tooth had a horizontal crown fracture at the cervical level and could not be restored. The tooth was extracted and processed for routine histological and immunohistochemical examination to identify the nature of tissues formed in the canal space. RESULTS: Clinically and radiographically, the revitalization of the present case was successful because of the absence of signs and symptoms and the resolution of periapical lesion as well as thickening of the canal walls and continued root development. The tissue formed in the canal was well-mineralized cementum- or bone-like tissue identified by routine histology and immunohistochemistry. No pulp-like tissue characterized by the presence of polarized odontoblast-like cells aligning dentin-like hard tissue was observed. CONCLUSIONS: The tissues formed in the canal of revitalized human tooth are similar to cementum- or bone-like tissue and fibrous connective tissue.

Expression and regulation of a disintegrin and metalloproteinase-8 and -17 in development of rat periradicular lesion.

INTRODUCTION: A disintegrin and metalloproteinases (ADAMs) are a family of transmembrane proteins that share a common domain structure. However, little is known about the possible involvement of ADAM-8 and ADAM-17 in the development of periradicular lesions. Here we demonstrated the expression of ADAM-8 and ADAM-17 in rat periradicular lesions. METHODS: We induced experimentally periradicular lesions in rats. The animals were killed at 0, 2, 4, 6, and 8 weeks after pulp exposure. The left molars underwent immunofluorescence analysis for both ADAMs and for neutrophil elastase, and right molars were used for reverse transcription-polymerase chain reaction analysis of ADAM-8 and ADAM-17. The areas of these lesions were measured histometrically, and the numbers of all antigen-positive cells in the periapical portion were counted per unit area. RESULTS: The area of the periradicular lesions gradually expanded from 0 to 4 weeks, showing a large increase from week 2 to week 4. Both ADAM-8-positive and ADAM-17-positive cells gradually increased in number from 0 to 4 weeks and then decreased from 4 to 8 weeks. There were more ADAM-17-expressing cells than ADAM-8-expressing ones at all experimental periods except at 4 weeks. The highest expression of ADAM-8 mRNA was observed at 4 weeks, and there were significant differences between 0 and 2 weeks and between 4 and 6 weeks. The expression of ADAM-17 mRNA increased from 0 to 4 weeks and subsequently decreased from 4 to 8 weeks, with a significant difference between 4 and 6 weeks. CONCLUSIONS: Our results suggest that ADAM-8 and ADAM-17 may be related to the development of rat periradicular lesions.