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 roles of autophagy and hypoxia in human inflammatory periapical lesions.

AIM: To determine the expressions of hypoxia-related [hypoxia-inducible transcription factors (HIF)-1α, BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) and phospho-adenosine monophosphate activated protein kinase (pAMPK)] and autophagy-related [microtubule-associated protein 1 light chain 3 (LC3), beclin-1 (BECN-1), autophagy-related gene (Atg)5-12, and p62] proteins in human inflammatory periapical lesions. METHODOLOGY: Fifteen samples of radicular cysts (RCs) and 21 periapical granulomas (PGs), combined with 17 healthy dental pulp tissues, were examined. Enzyme-linked immunosorbent assay (ELISA) was used to detect interleukin (IL)-1ß cytokine; immunohistochemical (IHC) and Western blot (WB) analyses were employed to examine autophagy-related and hypoxia-related proteins. Transmission electron microscopy (TEM) was used to explore the ultrastructural morphology of autophagy in periapical lesions. Nonparametric Kruskal-Wallis tests and Mann-Whitney U-tests were used for statistical analyses. RESULTS: ELISA revealed a significantly higher (P < 0.001) IL-1ß expression in periapical lesions than in normal pulp tissue. Immunoscores of IHC expressions of pAMPK, HIF-1α, BNIP3, BECN-1 and Atg5-12 proteins in periapical lesions were significantly higher (P < 0.001) (except BECN-1) than those in normal pulp tissue. The results of IHC studies were largely compatible with those of WB analyses, where significantly higher (P < 0.05) expressions of hypoxia-related and autophagy-related proteins (except BECN-1, p62 and LC3II in WB analyses) in periapical lesions were noted as compared to normal pulp tissue. Upon TEM, ultrastructural double-membrane autophagosomes and autolysosomes were observed in PGs and RCs. CONCLUSIONS: Autophagy associated with hypoxia may play a potential causative role in the development and maintenance of inflamed periapical lesions.

[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.

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.

Odontogenic cysts related to pulpotomized deciduous molars: clinical features and treatment outcome.

OBJECTIVE: The purpose of this study was to assess the morbidity and outcomes associated with large cysts that developed in conjunction with pulpotomized deciduous molars. STUDY DESIGN: This retrospective study was based on the files of 18 patients who were referred to 2 oral surgery departments during a 10-year period (1986-1996). The inclusion criteria were large cyst lesions (>1 cm in diameter) and complete documentation. Data regarding symptoms at presentation, histologic and radiologic features, treatment modalities, morbidity, and outcomes were analyzed. RESULTS: An equal gender distribution of patients was found, as were a later development in males (12+/-2 years in boys, 9+/-2 years in girls) and a 5:1 ratio favoring the mandible over the maxilla. Treatment included enucleation (12 patients) and marsupialization (6 patients). The morbidity was high and included loss of permanent teeth (3 patients), extensive loss of alveolar bone (3 patients), use of flaps (2 patients), and adjuvant orthodontic treatment (9 patients). CONCLUSION: Failure of early detection and treatment of cysts that develop in conjunction with pulpotomized deciduous molars can cause considerable morbidity. Therefore, periodic clinical and radiologic follow-up until the eruption of succedaneous teeth is recommended.

[Current methods of treating radicular cysts using a bioplant in a provincial dental polyclinic]. / Sovremennye metody lecheniia radikuliarnykh kist s ispol'zovaniem bioplanta v usloviiakh oblastnoi stomatologicheskoi polikliniki.

A Russian biological material from human placenta "bioplant" was used in 35 patients for repair of defects in the jaw bones after resection of dental apices and cystectomy. More rapid bone formation and a higher stability of teeth were observed than after traditional treatment (with osseointegration following the formation of a blood clot). Bioplant exerts an aseptic effect in a wound, possesses antiinflammatory and hemostatic effect, and causes no side or allergic reactions. Two types of incisions in this operation are compared. The L-shaped incision is preferable to traditional, as it helps escape complications in the postoperative period and attain better results.

Pulpal and periradicular response to caries: current management and regenerative options.

The pulp-dentin complex is a strategic and dynamic barrier to various insults that plague the dentition. Researchers have yet to understand the complete potential of this shifting junction and its components. The most common cause of injury to the pulp-dentin complex is carious breakdown of enamel and dentin. In recent years, there has been a change in restorative management of caries. The emphasis is on strategies to preserve dentin and protect the pulp. This article provides a brief review of the effect of caries on the pulp, of subsequent events on the periradicular tissues, and of current understanding of treatment modalities.

[Pathophysiological mechanism of the developing radicular cyst of the jaw].

The radicular cysts are result of inflammatory process in the periapical tissues associated with necrotic and infected pulps. Humoral and cellular immune responses play a central role in the pathogenesis of these lesions. The most important role in the growth of these lesion have proinflammatore cytokine TNF-alpha, IL-1 and IL-6. Cytokine can be secreted by macrophages, monocytes and other cells of the immune system and can participate in skeletal homeostasis including osteoclastic formation, and bone resorption in maxillofacial region. The aim of this study is to give a consise rewiew for mechanism of growth of maxilofacial radicular cysts, indicated of clinical aspect, as well as expalined role of cytokine in this pathophysiology process.

Epithelial jaw cysts: 10 years of the WHO classification.

Numerous papers on epithelial jaw cysts have appeared in the decade since the publication in 1971 of the WHO histological classification of odontogenic tumours, jaw cysts, and allied lesions. Despite clarification of certain cyst varieties no major revisions are necessary. The following minor modifications are proposed. In the developmental odontogenic group, the terms keratocyst and follicular are preferred to primordial and dentigerous. The alveolar cyst of infants is categorised separately from the gingival cyst of adults. The developmental lateral periodontal cyst is included as a distinctive new type. In the non-odontogenic group the globulomaxillary is deleted as a unique entity, whereas the midpalatal cyst of infants is a new inclusion. To the inflammatory category are added the inflammatory follicular and inflammatory lateral periodontal varieties.

Spontaneous bone regeneration after enucleation of large mandibular cysts: a radiographic computed analysis of 27 consecutive cases.

PURPOSE: This study evaluated the spontaneous bone healing after enucleation of large mandibular cysts subjectively and with a computed analysis of postoperative panoramic radiographs. PATIENTS AND METHODS: Twenty-nine patients had large mandibular cysts treated by surgical enucleation. Postoperative clinical and radiographic examinations were performed at 6, 12, and 24 months in 27 patients. Bone regeneration and reduction of the residual cavities and bone density were evaluated with a computed analysis of preoperative and postoperative panoramic radiographs. A subjective and clinical radiographic evaluation of the healing process also was performed. RESULTS: Uneventful healing and spontaneous filling of the residual cavities was obtained in all cases. The computed analysis of the postoperative radiographs showed mean values of reduction in size of the residual cavity of 12.34% after 6 months, 43.46% after 12 months, and 81.30% after 24 months. The increase in bone density was 37% after 6 months, 48.27% after 12 months, and 91.01% after 24 months. CONCLUSION: Spontaneous bone regeneration can occur in large mandibular cysts without the aid of any filling materials. This simplifies the surgical procedure, decreases the economic and biologic costs, and reduces the risk of postoperative complications.

Osteolytic processes in human radicular cysts: morphological and biochemical results.

In an attempt to verify the nature of bone resorption processes on the bone surrounding radicular cysts, fragments of cysts with the adjacent bone tissue were studied by morphological, cytochemical and ultrastructural methods. Cyst fluid was analysed for its content of cytokines with osteolytic activity. The cyst wall exhibited several connective tissue extensions which penetrated the adjacent bone. Numerous multinucleated tartrate-resistant acid phosphatase (TRAP)-positive cells were seen at the tip of the intraosseous extensions of the cyst capsule and in direct contact with the bone tissue. Typical resorption lacunae were identified on the bone surface by scanning electron microscopy. Moreover, mononuclear TRAP-positive cells were seen within the cyst capsule. High levels of prostaglandin E2 (PGE2) and interleukin-6 (IL-6) were detected in the cyst fluids. In conclusion, active bone resorption may contribute significantly to the growth of these lesions within the jaws.

Immunocytochemical localization of inflammatory cytokines and vascular adhesion receptors in radicular cysts.

Odontogenic cysts are one of the commonest bone destroying lesions of the maxillofacial skeleton, with the inflammatory radicular cyst being the commonest jaw cyst. Explants of radicular cysts produce an interleukin-1-like activity which could explain the osteolysis seen with these tumours though the cellular source of this osteolytic activity is unknown. In the present study, cytokines with known inflammatory and osteolytic activity: interleukin-1 (IL-1), tumour necrosis factor (TNF), interleukin-6 (IL-6), and the chemotactic cytokine interleukin-8 (IL-8) have been localized immunocytochemically in radicular cysts. The cellular adhesion receptors ICAM-1 and ELAM-1 have also been immunolocalized. All specimens showed positive staining for IL-1 (alpha and beta) and IL-6, with these cytokines being located in epithelial and vascular endothelial cells. Only two specimens demonstrated TNF and IL-8 staining, which was located in macrophages. All specimens demonstrated ELAM-1 staining in endothelium and ICAM-1 staining in epithelium, endothelium and mononuclear cells. These findings show that radicular cysts contain two bone-modulating cytokines, IL-1 and IL-6, and that these appear to be synthesized mainly by the epithelial cells. Cysts also contain a proportion of activated blood vessels whose endothelial cells express the cellular adhesion receptors ICAM-1 and ELAM-1.

Features of odontogenesis and expression of cytokeratins and tenascin-C in three cases of extraosseous and intraosseous calcifying odontogenic cyst.

To characterize further the nature of calcifying odontogenic cyst (COC), we studied histologically and immunohistochemically an extraosseous and two intraosseous lesions. The extraosseous COC was in continuity with the stratified squamous epithelium of the alveolar mucosa. Immunostaining with monoclonal antibodies showed reactivity of both low- and high-molecular-weight cytokeratins, the degree of coexpression decreasing with the increasing morphological diversity of the cyst/tumour epithelium. Staining for the matrix glycoprotein tenascin-C was seen not only in the connective tissue, where its distribution patterns corresponded to the stage of hard tissue formation, but also in epithelial elements. The staining patterns were analogous to those described during normal tooth formation. Both the morphological characteristics and expression patterns of the various cytokeratin types and tenascin-C implied that COC represents a pathological counterpart of normal odontogenesis. In the case of the extraosseous COC, the correspondence could be traced back to early stages of tooth development.

Mecanismos imunopatológicos de formaçäo e expansäo do cisto radicular: uma abordagem atual / Immunopathological mechanisms involved in the growth and expansion of radicular cysts

Os cistos radiculares constituem lesöes ósteo-destrutivas que comumente acometem os ossos maxilares, visto que sua patogenia se relaciona a eventos imuno-inflamatórios posteriores à necrose pulpar. O propósito deste trabalho consiste em apresentar uma revisäo dos aspectos etiopatogenéticos do cisto radicular, com especial mençäo aos mecanismos imunopatológicos envolvidos no processo de crescimento e expansäo cística