Inflammatory Response Mechanisms of the Dentine-Pulp Complex and the Periapical Tissues.

The macroscopic and microscopic anatomy of the oral cavity is complex and unique in the human body. Soft-tissue structures are in close interaction with mineralized bone, but also dentine, cementum and enamel of our teeth. These are exposed to intense mechanical and chemical stress as well as to dense microbiologic colonization. Teeth are susceptible to damage, most commonly to caries, where microorganisms from the oral cavity degrade the mineralized tissues of enamel and dentine and invade the soft connective tissue at the core, the dental pulp. However, the pulp is well-equipped to sense and fend off bacteria and their products and mounts various and intricate defense mechanisms. The front rank is formed by a layer of odontoblasts, which line the pulp chamber towards the dentine. These highly specialized cells not only form mineralized tissue but exert important functions as barrier cells. They recognize pathogens early in the process, secrete antibacterial compounds and neutralize bacterial toxins, initiate the immune response and alert other key players of the host defense. As bacteria get closer to the pulp, additional cell types of the pulp, including fibroblasts, stem and immune cells, but also vascular and neuronal networks, contribute with a variety of distinct defense mechanisms, and inflammatory response mechanisms are critical for tissue homeostasis. Still, without therapeutic intervention, a deep carious lesion may lead to tissue necrosis, which allows bacteria to populate the root canal system and invade the periradicular bone via the apical foramen at the root tip. The periodontal tissues and alveolar bone react to the insult with an inflammatory response, most commonly by the formation of an apical granuloma. Healing can occur after pathogen removal, which is achieved by disinfection and obturation of the pulp space by root canal treatment. This review highlights the various mechanisms of pathogen recognition and defense of dental pulp cells and periradicular tissues, explains the different cell types involved in the immune response and discusses the mechanisms of healing and repair, pointing out the close links between inflammation and regeneration as well as between inflammation and potential malignant transformation.

[The radicular cyst in the maxillary sinus encountered in the clinical otorhinolaryngological practice]. / Radikuliarnaia kista verkhnei cheliusti v praktike otorinolaringologa.

This article was designed to report the clinical case of the radicular cyst localized in the maxillary sinus of the 23 year-old man that had been detected before the surgical intervention was undertaken for its treatment. In the preceding visits of the patient to other medical settings, this condition was misinterpreted as a genuine (rhinogenic) cyst. It accounted for the choice of the inadequate surgical strategy for the management of this pathology. As a result, the patient experienced two relapse episodes of the disease. The thorough analysis of the patient's medical history and CT images of the sinus obtained during the 4 year follow up period allowed to establish the definitive diagnosis of odontogenic cyst of the upper jaw. The authors present a brief overview of the relevant scientific literature concerning etiology and pathogenesis as well as the methods of diagnostics and treatment of radicular cyst of the upper jaw.

Association between odontogenic infections and unilateral sinus opacification.

OBJECTIVES: Consideration of the causes of unilateral paranasal sinusitis, which frequently occurs in routine medical care and is often associated with odontogenic infection. STUDY DESIGN: Retrospective data analysis. METHODS: A review of the charts of all 190 patients treated for unilateral paranasal sinusitis at our department between 2005 and 2012 was carried out. All patients were diagnosed based on clinical signs, symptoms, and imaging findings, including computed tomography (CT), orthopantomography (OP), and other modalities. Patients were classified in three groups: patients with odontogenic infection involvement (Group A); patients without odontogenic infection involvement (Group B); and patients with inconclusive odontogenic infection involvement (Group C). RESULTS: The most common cause of unilateral paranasal sinusitis was odontogenic infection, as seen in 138 cases (72.6%), followed by chronic inflammation in 43 cases (22.6%). Among patients diagnosed with odontogenic infection, one patient was also diagnosed with coexistent polyps and mycosis. Based on CT, OP, EPT, and oral examination, final distribution was 138 patients (72.6%) in Group A, 32 (16.8%) in Group B, and 20 (10.5%) in Group C. CONCLUSIONS: Odontogenic infection involvement was implicated in approximately 70% cases of unilateral paranasal sinusitis. Odontogenic maxillary sinusitis can be difficult to diagnose, and consideration of imaging performed under various conditions is recommended. In order to determine the most appropriate treatment for unilateral paranasal sinusitis, whether such treatment will be surgery, dental treatment, conservative therapy, or other treatments, collaboration between concerned doctors is essential.

Role of matrix metalloproteinases in radicular cysts and periapical granulomas.

AIM: The aim of the present study was to evaluate the expression and distribution of different classes of matrix metalloproteinases (MMPs) in radicular cysts and periapical granulomas. METHODS: Twenty consecutive specimens of radicular cysts and 20 of periapical granulomas were selected. Expression of MMP-2, -9, -8, -13, -3 was immunohistochemically evaluated. The intensity of expression of the MMPs was evaluated using a semi-quantitative analysis: low = +; intermediate = ++; high = +++. RESULTS: Positive expression of MMPs was present with different distribution. MMP-9 expressed differently in the lesions. Indeed, in periapical granulomas low expression was found in endothelial cells and fibroblasts, whilst high intensities were only detected in inflammatory cells. On the contrary, in radicular cysts the high intensities were mainly present in keratinocytes and fibroblasts. MMP-8 was mainly expressed in inflammatory cells of periapical granulomas. MMP-2 and -3 presented a low intensity of expression in both groups. MMP-13 showed a variable pattern of distribution in the different cell types of the two different lesions. CONCLUSION: The present investigation supports the role of MMPs in the inflammatory process leading to the development of radicular cysts and periapical granulomas. The results of the present study suggested that the increased enlargement of radicular cysts, compared to periapical granulomas, might be related to a higher expression of MMP-9. On the other hands, the higher intensity of expression of MMP-8 in periapical granulomas could be related to an active inflammatory process. MMP-8 could play an important role in the inflammation processes during the development of periapical lesions.

Possible role of apoptosis in the pathogenesis and clinical evolution of radicular cyst: an immunohistochemical study.

AIM: To investigate whether the apoptotic cascade is activated through the extrinsic pathway in epithelial lining and connective tissue of radicular cysts. METHODOLOGY: Fifteen radicular cysts were fixed in formalin, embedded in paraffin wax and processed for immunohistochemistry to evaluate the expression of polyclonal antibodies against Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), DR5 and caspase-3. Immunocomplexes were treated with the secondary antibodies and finally detected using the avidin-biotin-peroxidase complex. Immunoreactivity was visualized by development with 3,3'-diaminobenzidine. Data were analysed using the Mann-Whitney U-test; P < 0.05 was considered significant. RESULTS: The three antibodies were detected in connective tissue fibroblasts of all radicular cysts; TRAIL and DR5 immunoexpression was significantly greater (P < 0.05) compared with that of caspase-3. The three antibodies were also expressed in almost all epithelial layers and in endothelial cells of newly formed vessels. CONCLUSION: The involvement of apoptosis in the pathogenesis of radicular cysts, demonstrated by the immunoexpression patterns of TRAIL, DR5 and caspase-3 in lining epithelium and connective tissue, may explain their bland clinical aggressiveness and slow, benign evolution.

Can traumatic occlusion cause endodontic problems? A case report.

Radicular cysts are commonly found odontogenic cysts in the jaws. The lesion is diagnosed mainly in young patients during the second decade of life. In the majority of cases, it is asymptomatic. This paper reports a rare case in which traumatic occlusion was identified as the etiology of a radicular cyst. Endodontic treatment was performed and the traumatic occlusion also was corrected. A six-month follow-up appointment found good healing of the periapical region.

Mixed periapical lesion: differential diagnosis of a case.

A radicular cyst associated with carious teeth is a very common odontogenic lesion in the oral cavity, but calcifications in residual radicular cysts are quite rare. We report one such case where a routine pre-implant radiographic assessment revealed a mixed periapical radiopaque radiolucent lesion in the right maxillary central incisor region. Histological and radiographic studies show that there is a slow increase in the mineralized deposits within the cyst lumen with time. This becomes prominent histochemically in cysts more than 8 years old and radiographically 6 years later, as seen in our case. In this paper we would like to highlight the importance of a residual radicular cyst with calcifications in the differential diagnosis of a mixed periapical radiopaque radiolucent lesion.

Unusual presentation of active implant periapical lesions: a report of two cases.

Active implant periapical lesion (IPL) is a rare lesion which has been reported as one of the causes of dental implant failures. Usually, an affected implant shows radiolucency in the apical area, while remaining clinically stable. IPL is often accompanied by symptoms of pain, swelling, tenderness, and fistulation. In this paper, we describe two cases of IPL with very unusual findings which led to implant failure. A large IPL associated with an inflammatory cyst in the anterior maxilla, and a mandibular IPL resulting in an extra-oral fistula are presented. The etiology and treatment approaches for IPL are discussed.

Lack of periradicular healing and gradually increasing swelling two years after intentional extrusion of calcium hydroxide into periapical lesion: report of a case.

A 40-year-old female patient with noncontributory medical history presented to the postgraduate clinic of the Department of Endodontology, Aristotle University of Thessaloniki, Greece. Her chief complaint was a gradually increasing swelling in the left side of her maxilla, during the preceding 2 months. After clinical examination, the radiologic and computerized tomographic scan examinations revealed the presence of a radiopaque foreign material in contact with the apex of tooth #22, confined within the limits of a radiolucent area. On dental anamnesis and after communication with her dentist, it was concluded that calcium hydroxide was deliberately extruded for the healing of the large lesion. The patient was scheduled for periapical surgery. The histopathologic features of the lesion revealed the presence of a periapical cyst and the absence of foreign body giant cells. After an observation period of 1 year, healing was uneventful.

Role of interleukin-1 in pathogenesis of radicular cyst.

BACKGROUND: Interleukin-1 (IL-1) is one of the cytokines produced by macrophages, monocytes and dentritc cells. Macrophages are present in apical granuloma and the wall of the radicular cyst. This cytokine causes the cyst expansion and is involved in proliferation of fibroblasts in the cyst wall and stimulate the fibroblasts to produce more prostaglandin. Radicular cyst is the most common cyst of the jaws which is usually associated with necrotic pulp of the tooth. The cyst formation requires proliferation of the epithelial rest cells of Malassez present in the periodontal ligament. Proliferation of epithelial rest cells of Malassez is an essential event in the Pathogenesis of radicular cyst. Objective of the study was to investigate the effect of IL-1 on epithelial cell proliferation which is an important factor in the pathogenesis of radicular cyst. METHODS: The cyst walls of 20 radicular cysts were removed and were cultured in vitro to grow the epithelial cells. The culture were rapidly contaminated and dominated by growth of fibroblasts. Therefore another cell line was used for the experiments. RESULTS: The result showed that proliferation was stimulated with increased in a biphasic manner with maximum stimulation at 1.25 nanog/ml, beyond this concentration proliferation was decreased. CONCLUSION: IL-1 had a proliferative effect on epithelial cells at low concentrations which may be playing a role in evoking an inflammatory reaction and stimulating the epithelial cell rests of Malassez to proliferate to form radicular cyst.

Histopathological profile of surgically removed persistent periapical radiolucent lesions of endodontic origin.

AIM: To determine the types of periapical lesions associated with root filled teeth with persistent periapical pathosis that required surgical treatment based on specific inclusion and exclusion criteria. METHODOLOGY: Periapical lesions from a consecutive clinical sample of 100 patients were examined histopathologically to determine a definitive diagnosis. RESULTS: Females were more represented (n = 56), the average age was 46.5 years and there were no age differences between gender or lesion type. A diagnosis of periapical granuloma was the most common finding with a similar number present in females (n = 40) and males (n = 37). A cyst was present in 18% of the cases with a majority of females (n = 12) represented in the sample. Evidence of foreign material, with an appearance consistent with endodontic sealer materials, was seen in 25 periapical granulomas, two cysts and one scar. Two periapical scars were seen, one had a history of apicectomy and amalgam root-end filling while the other was associated with extruded root filling material. CONCLUSIONS: By using defined clinical inclusion and exclusion criteria a predictable clinical diagnosis of a persistent periapical lesion due to endodontic origin can be reliably made. Periapical granulomas and cysts were the most common periapical lesions of endodontic origin associated with persistent periapical pathosis with the overall incidence of periapical cysts similar to previous studies. The presence of endodontic material in a high proportion of periapical lesions suggests a cause-effect association with the inference that clinicians should employ canal preparation techniques that limit apical extrusion of material.

Experimental evidence supports the abscess theory of development of radicular cysts.

OBJECTIVE: The objective of this study was to experimentally induce inflammatory cysts in an animal model so as to test the hypothesis that radicular cysts develop via the "abscess pathway." METHODOLOGY: Twenty-eight perforated custom-made Teflon cages were surgically implanted into defined locations in the back of 7 Sprague Dawley rats. A week after the implantation of the cages, a known quantity of freshly grown, close allogeneic oral keratinocytes in phosphate buffer solution (PBS) was injected into each cage. One cage per animal was treated as the control that received only epithelial cells. The remaining 3 cages of each animal were trials. Seven days post epithelial cell inoculation; a suspension of 0.2 mL of Fusobacterium nucleatum (10(8) bacteria per mL) was injected into each of the 3 trial cages. Two, 12, and 24 weeks after the inoculation of the bacteria, the cages were taken out, and the tissue contents were fixed and processed by correlative light and transmission electron microscopy. Sixteen of the 21 trial cages could be processed and yielded results. RESULTS: Inoculations of epithelial cells followed 1 week later by F. nucleatum into tissue cages resulted in the development inflammatory cysts in 2 of the 16 cages. The 2 cages contained a total of 4 cystic sites. None of the control cages showed the presence of any cyst-like pathology. CONCLUSIONS: Inflammatory cysts were induced by initiating acute inflammatory foci (abscess/necrotic area) by bacterial injection that got enclosed by a proliferating epithelium. This finding provides strong experimental evidence in support of the "abscess theory" of development of radicular cysts.

Cytokine and chemokine levels in radicular and residual cyst fluids.

BACKGROUND: Cytokines were thought to play an important role for the expansion of odontogenic cysts. The purpose of this study was to evaluate the cytokine and chemokine levels of radicular and residual cyst fluids. METHODS: Cyst fluids were aspirated from 21 patients (11 radicular and 10 residual cysts) and the levels of interleukin-1 alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), and regulated upon activation normal T cell expressed and secreted (RANTES) were determined by ELISA using commercially available kits. RESULTS: Both radicular and residual cyst fluids contained IL-1alpha, TNF-alpha, MCP-1, and RANTES, concentrations of which were significantly higher in the radicular cyst fluids than those in the residual cysts (P < 0.001 for IL-1alpha, TNF-alpha, and RANTES; P < 0.01 for MCP-1). Compared to the other mediators, the concentration of IL-1alpha was found to be highest in both of the cyst fluids. In addition, positive correlations were found between IL-1alpha, TNF-alpha, MCP-1, and RANTES in radicular and residual cyst fluids. CONCLUSION: If the radicular cyst is inadvertently left behind following tooth extraction, some degree of inflammation may carry on. Residual cysts, although to a lesser extend than radicular cysts, have the potential to expand.

Spontaneous alignment of permanent successors after enucleation of odontogenic cysts associated with primary teeth.

Pulpotomy and pulpectomy occasionally lead to cyst formation in the primary dentition. They show specific clinical features of large size, rapid growth, buccal expansion and displacement of permanent teeth. Complete enucleation of the cyst with extraction of the associated primary teeth and preservation of the permanent teeth appeared to be the most suitable treatment option. Normal alignment of the permanent teeth occurred spontaneously even their initial positions were highly unfavourable.

Proliferation of epithelial cell rests, formation of apical cysts, and regression of apical cysts after periapical wound healing.

There is continuing controversy regarding the potential for inflammatory apical cysts to heal after nonsurgical endodontic therapy. Molecular cell biology may provide answers to a series of related questions. How are the epithelial cell rests of Malassez stimulated to proliferate? How are the apical cysts formed? How does the lining epithelium of apical cysts regress after endodontic therapy? Epithelial cell rests are induced to divide and proliferate by inflammatory mediators, proinflammatory cytokines, and growth factors released from host cells during periradicular inflammation. Quiescent epithelial cell rests can behave like restricted-potential stem cells if stimulated to proliferate. Formation of apical cysts is most likely caused by the merging of proliferating epithelial strands from all directions to form a three-dimensional ball mass. After endodontic therapy, epithelial cells in epithelial strands of periapical granulomas and the lining epithelium of apical cysts may stop proliferating because of a reduction in inflammatory mediators, proinflammatory cytokines, and growth factors. Epithelial cells will also regress because of activation of apoptosis or programmed cell death through deprivation of survival factors or by receiving death signals during periapical wound healing.

Formación de los granulomas y quistes radiculares: una revisión de los aspectos inmunopatológicos / Formation of granulomas and radicular cysts: a review of the immunopathological aspects

Los granulomas y quistes radiculares representan lesiones crónicas que comprometen la región perirradicular, consideradas secuelas directas de la necrosis pulpar. El estudio de tales lesiones adquiere una importancia particular en la práctica odontológica debido a su alta frecuencia clínica. Este artículo presenta una revisión de la literatura sobre los principales eventos que llevan a la formación del granuloma periapical y la posterior formación de cavidades quísticas, dándole énfasis especial a los mecanismos inmunopatológicos relacionados con la patogénesis de tales lesiones.

Nonsurgical treatment of extensive cyst-like periapical lesion of endodontic origin.

AIM: To report the repair of an extensive periapical lesion of endodontic origin, following nonsurgical treatment. SUMMARY: Clinical and radiographic examination revealed an extensive periapical lesion related to tooth 22, extending from the distal surface of tooth 21 to the mesial surface of 26. The patient reported a previous history of dental trauma involving this quadrant and had been under orthodontic treatment for a year. Intraoral examination revealed an asymptomatic bony hard swelling, mainly confined to the palate. During root canal exploration irregular walls associated with 3 mm of apical calcification were noted. After apical patency was obtained 1 mL of bloody serous exudate was drained. Intracanal aspiration provided a further 2 mL of yellow serous exudate. Following biomechanical preparation, a dressing of calcium hydroxide with anaesthetic solution was applied and replaced four times over a period of 12 months. The clinical-pathological picture demonstrated resolution of the lesion during this period of time. The 14-month clinical and radiographic examinations revealed normal bony contour and a significant resolution of the maxillary radiolucency. KEY LEARNING POINTS: Periapical lesions of endodontic origin may develop asymptomatically and become large. Proper biomechanical preparation followed by calcium hydroxide medication renewed periodically represents a nonsurgical approach to resolve extensive inflammatory periapical lesions.

Complications following replantation of a primary incisor: a cautionary tale.

The replantation of avulsed primary incisors is contra-indicated. This case describes an 8-year-old child who six years previously had avulsed and had replanted a primary central incisor. At presentation, this tooth was retained, the permanent successor had failed to erupt and appearance of the adjacent lateral incisor was notably delayed. Investigation revealed a radicular cyst in relation to the replanted deciduous incisor together with severe displacement of the permanent tooth, which could not be saved.

Radicular cyst arising from a traumatized primary incisor: a case report of a rare complication that emphasizes the need for regular follow up.

Radicular cysts associated with the deciduous dentition are rare. The literature is sparse regarding cysts associated with primary incisor teeth, which is surprising given the frequency with which these teeth are traumatized. Most cases reported involve molar teeth associated with apical infection following on from caries. A case of a 3-year-old boy who developed a large radicular cyst associated with a previously traumatized upper primary incisor is reported.

Cisto odontogênico botrióide: relato de um caso / Botryoid odontogenic cyst: report of a case

O cisto odontogênico botrióide (COB) é uma lesão incomum dos ossos maxilares esporadicamente relatada na literatura, considerada uma variante multicística do Cisto Periodontal Lateral em virtude de sua apresentação microscópica. Apesar da maioria dos relatos de COB descreverem-no como uma imagem radiolúcida multilocular, alguns autores têm destacado que esta lesão também pode apresentar-se como uma imagem unilocular, assemelhando-se, assim, a várias outras entidades odontogênicas císticas ou neoplásicas. O objetivo deste artigo é relatar um caso de COB localizado na região posterior esquerda da mandíbula de uma mulher de 53 anos cuja apresentação radiográfica simulava um cisto periapical residual. As características clínicas, radiográficas e histopatológicas da lesão, bem como a abordagem terapêutica escolhida, são descritos, ao passo que algumas considerações acerca da histogênese, diagnóstico diferencial e comportamento biológico dessa entidade são tecidas e discutidas