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.

Traumatic ulcerative granuloma with stromal eosinophilia around mini dental implants without the protection of a denture base.

This is a report of a case of an unusual oral lesion after the placement of mini implants for the retention of a mandibular overdenture. A patient received four 2-mm-wide dental implants in the anterior mandible and had her mandibular denture relined with a soft material. After 3 months, she was not wearing her mandibular denture, and two nodular ulcerated lesions were observed near the mini implants. The lesions ceased following excision and regular denture wearing. Clinical and microscopic examination led to the diagnosis of traumatic ulcerative granuloma with stromal eosinophilia (TUGSE). TUGSE is rare lesion with a benign course that may occur following injury of the oral mucosa by mini implants under certain circumstances.

Mesenchymal stem cells as active prohealing and immunosuppressive agents in periapical environment: evidence from human and experimental periapical lesions.

INTRODUCTION: Previous studies describe contrasting molecular profiles of active and inactive periapical granulomas characterized by distinct expression of cytokines, osteoclastogenic factors, and wound healing markers. Although the molecular mechanisms underlying such a dichotomy remain unknown, in this study we investigated the potential involvement of mesenchymal stem cells (MSCs) in determining human and murine periapical lesion activity and outcomes. METHODS: Periapical granulomas (n = 83) and control samples (n = 24) were comparatively assessed for the expression levels of 11 mesenchymal stem cell (MSC) markers using real-time polymerase chain reaction. Experimental periapical lesions induced in mice were evaluated for MSC marker expression and the effects of AMD3100 treatment on lesion outcomes. RESULTS: MCS marker expression was prevalent in periapical granulomas compared with that in controls, whereas CD29, CD73, CD90, CD146, CD166, NANOG, Stro-1, and CXCR4 expressions were higher in inactive than in active lesions. Experimental periapical lesion inactivity was also associated with an increased expression of MSC markers. The inhibition of MSC mobilization to the periapex by AMD3100 resulted in increased lesion sizes; decreased expression of MSCs and wound healing markers; and increased expression of interleukin 1 beta (IL-17ß), interleukin 17 (IL-17), tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and nuclear factor kappa-B ligand (RANKL). CONCLUSIONS: Our results show that MSC markers are overexpressed in inactive human and experimental periapical lesions and that MSC mobilization results in the attenuation of experimental lesion progression associated with immunosuppressive and prohealing mechanisms.

[Histopathology and etiopathogenesis of chronic apical periodontitis--periapical granuloma]. / Histopatológia a etiopatogenéza chronickej apikálnej parodontitídy--periapikálnych granulómov.

Periapical lesions are among the most frequently diagnosed apical odontogenic pathologies in human teeth. The condition is generally described as apical periodontitis. Apical periodontitis is a sequel to endodontic infection and manifests itself as the host defense response to microbial challenge emanating from the root canal system to the periapical tissue. It is viewed as a dynamic encounter between microbial factors and host defenses at the interface between infected radicular pulp and periodontal ligament that results in local inflammation, resorption of hard tissues, destruction of other periapical tissues, and eventual formation of various histopathological categories of apical periodontitis, commonly referred to as periapical lesions. There are also factors located within the inflamed periapical tissue that can interfere with post-treatment healing of the lesion. The purpose of this article is to provide a comprehensive overview of the etiopathogenesis of apical periodontitis and causes of failed endodontic treatment. This study presents a histopathological analysis through optical microscopy of periapical lesions, commonly referred to as solid dental or periapical granuloma.

Regression of a lesion resembling pyogenic granuloma after endodontic treatment.

A rare case of regression of a lesion resembling pyogenic granuloma after endodontic treatment of a maxillary lateral incisor in a 16-year-old female patient is reported. After clinical and radiographic examination, the maxillary right lateral incisor was endodontically treated in two visits. At the second visit, clinical regression of the exophytic lesion was evident and the size of this lesion had been greatly decreased, so was not biopsied. After 3 weeks, the exophytic lesion had totally disappeared. This case report indicates that surgical excision of exophytic lesions resembling pyogenic granuloma is not necessary in all situations.

Macrophages in periapical lesions.

Macrophages are major constituents of periapical granulomas. They have a central protective role in both innate immunity and adoptive, antigen-specific immune response. Macrophage activation may occur in periapical granulomas by cytokines produced by antigen-activated T-lymphocytes; by bacterial endotoxin, as part of the innate immunity; or by both these processes. Recent studies in athymic animals have shown that periapical granulomas may develop independently of T-lymphocytes. This observation reveals the major role that the activated macrophage may have in the formation of periapical lesions. Only a few of the macrophages in the periapical granuloma are activated. Current studies indicate that these activated cells are the source of the bone-resorbing cytokines in the periapical granuloma. Understanding the central role of the activated macrophage in the formation as well as the perpetuation of periapical lesions may lead to the development of new diagnostic and therapeutic tools in endodontics.

[The role of cell adhesion molecules in the formation of periapical granulomas]. / Ruolo delle molecole di adesione cellulare nella formazione dei granulomi periapicali.

Cell adhesion molecules (CAMs) are cell surface proteins involved in the binding of cells, usually leukocytes, to each other, to endothelial cells, or to extracellular matrix. Specific signals produced in response to wounding and infection control the expression and activation of certain of these adhesion molecules. The interactions and responses then initiated by binding of these CAMs to their receptors/ligands play important roles in the mediation of the inflammatory and immune reactions that consult one line of the body's defense against these insults. Most of the CAMs characterized so far fall into three general families of proteins: the immunoglobulin (Ig) superfamily, the integrin family, or the selectine family. Recent studies have indicated that selectins (E,L,P) are implicated in cell trafficking, an important aspect of inflammation-related process. Regulation of white blood cell trafficking from the blood vascular compartment to regions of pathogenic exposure is one of the most important functions of the immune system. The distinct phases of leukocyte migration include: rolling, activation, firm adhesion, transendothelial migration and subendothelial migration. The selectins have been implicated in the first step of this cascade. An inflammatory response is first evoked in the pulpal tissue in an attempt to neutralize the injurious agent and to dispose of damaged tissue and cells. The pulpal vessels dilate and blood flow to the tooth increases. At the same time, permeability of the vessels increases allowing leakage of fluid and leukocytes into the tissue.

Characterization of bone-resorbing activity in human periapical lesions.

Extracts of human periapical granulomas were tested for the presence of bone-resorbing activity. All granulomas (10 of 10) contained low but significant levels of bone-resorbing activity, ranging from 2.1 to 4.9% treatment-% control/mg specific 45Ca release, as determined by the fetal rat long bone assay. Healthy periodontal ligament and dental pulp had no significant resorbing activity. In characterization studies, the resorbing activity in an extract pool was unaffected by the presence of polymyxin B, indicating an active moiety distinct from lipopolysaccharide. Resorbing activity was also unaffected by heating to 56 degrees C for 30 min, but was completely abolished by proteinase K treatment or heating to 70 degrees C, indicating that activity was largely protein mediated. Fast performance liquid chromatography gel filtration studies demonstrated that activity could be resolved to two major peaks, of M(r) 30,000 to 60,000 (I), and 15,000 to 20,000 (II), with a minor peak present at < 1,000 (III). Peak III was identified as prostaglandin E2 by radioimmunoassay. In inhibition studies, virtually all of the resorbing activity present was inhibited by anti-interleukin 1 beta (69%) and anti-tumor necrosis factor beta (66%) antisera, whereas anti-interleukin 1 alpha and antitumor necrosis factor alpha had no effect. Treatment with the cyclooxygenase inhibitor indomethacin also reduced activity by 74%. Taken together, these data demonstrate that most bone-resorbing activity present in chronic human periapical lesions is attributable to the action of resorptive cytokines interleukin 1 beta and tumor necrosis factor beta, acting via both indomethacin-dependent and independent pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

[Periodontal function and oral hygiene following an operation for apicoectomy]. / Funktsional'noe sostoianie parodonta i gigiena polosti rta posle operatsii rezektsii verkhushki kornia zuba.

The author analyzes the effect of the dental root apex resection on the function of marginal periodontal tissues of the operated on tooth and oral hygiene of 103 patients with chronic periapical foci of odontogenic infection, aged 12 to 53, on the basis of the data of monitoring the changes in the content of gingival fluid, depth of the gingival grooves or pouches, and the Schiller-Pisarev test and hygiene index. The operation in question was found to essentially disorder the biologic equilibrium in the marginal periodontal tissues and to deteriorate the hygienic status of the oral cavity. The developing shifts are reversible and disappear in two weeks after surgery. The author emphasizes that such patients should be timely trained to take care of the oral cavity in order to improve its hygienic status in the postoperative period.

[Mastocytes and the oral cavity. Anatomy and function]. / Mastocytes et cavité buccale. Anatomie et fonction.

One hundred and three teeth with chronic pulpitis, twelve chronic periapical lesions and eleven oral various soft tissue biopsies were used to discuss the presence, the anatomy and function of mast cells. The mast cell induces veinules dilatation during the early phase of inflammation by histamine release, collagen lysis, bone resorption and epithelium proliferation. It can be observed in every chronic lesion and plays a part in both humoral and cellular immunological phenomenons. A more accurate knowledge of its biochemical actions could help in understanding the mechanism of pain in certain clinical dental crisis.