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Objective: To evaluate the effect of casein supplementation on the periodontium and mandibular bone of rats fed a standard diet and a cafeteria diet. Methodology: 24 Wistar rats were divided into four experimental groups: normal diet (DN), normal diet with casein (DNC), cafeteria diet (DC) and cafeteria diet with casein (DCC). The DNC and DCC groups received 2 mL of micellar casein from the 60th to the 90th day. At 90 days, the animals were orthouthanized and the materials were collected for analysis. Results: The animals in the DC and DCC groups showed a higher adiposity index compared to DN and DNC (p

Periodontal disease (PD) is a chronic destructive inflammatory disease of the tooth-supporting structures that leads to tooth loss at its advanced stages. Although the disease is initiated by a complex organization of oral microorganisms in the form of a plaque biofilm, it is the uncontrolled immune response to periodontal pathogens that fuels periodontal tissue destruction. IL-17A has been identified as a key cytokine in the pathogenesis of PD. Despite its well documented role in host defense against invading pathogens at oral barrier sites, IL-17A–mediated signaling can also lead to a detrimental inflammatory response, causing periodontal bone destruction. In this study, we developed a local sustained delivery system that restrains IL-17A hyperactivity in periodontal tissues by incorporating neutralizing anti–IL-17A Abs in poly(lactic-coglycolic) acid microparticles (MP). This formulation allowed for controlled release of anti–IL-17A in the periodontium of mice with ligature-induced PD. Local delivery of anti–IL-17A MP after murine PD induction inhibited alveolar bone loss and osteoclastic activity. The anti–IL-17A MP formulation also decreased expression of IL-6, an IL-17A target gene known to induce bone resorption in periodontal tissues. This study demonstrates proof of concept that local and sustained release of IL-17A Abs constitutes a promising therapeutic strategy for PD and may be applicable to other osteolytic bone diseases mediated by IL-17A–driven inflammation.

Submitted by azevedo@ufp.pt (azevedo@ufp.pt) on 2019-03-15T13:49:34Z No. of bitstreams: 1 PPG_29220.pdf: 210188 bytes, checksum: 0e3ffdf4c60eb715aafbdc7695332494 (MD5) Approved for entry into archive by halves@ufp.pt (halves@ufp.pt) on 2019-03-15T14:00:27Z (GMT) No. of bitstreams: 1 PPG_29220.pdf: 210188 bytes, checksum: 0e3ffdf4c60eb715aafbdc7695332494 (MD5) Made available in DSpace on 2019-03-15T14:00:27Z (GMT). No. of bitstreams: 1 PPG_29220.pdf: 210188 bytes, checksum: 0e3ffdf4c60eb715aafbdc7695332494 (MD5) Previous issue date: 2018-09-25

Aim Leukotrienes (LTs) are pro-inflammatory lipid mediators formed by the enzyme 5-lipoxygenase (5-LO). The involvement of 5-LO metabolites in periodontal disease (PD) is not well defined. This study aimed to assess the role of 5-LO in experimental PD induced by Aggregatibacter actinomycetemcomitans (Aa). Material and Methods In vivo experiments were carried out using SV129 wild-type (WT) and 5-LO-deficient (5lo-/-) mice inoculated with Aa. Osteoclasts were stimulated in vitro with AaLPS in the presence or not of selective inhibitors of the 5-LO pathway, or LTB4 or platelet-activating factor (PAF), as PAF has already been shown to increase osteoclast activity. Results In 5lo-/- mice, there were no loss of alveolar bone and less TRAP-positive osteoclasts in periodontal tissues, after Aa inoculation, despite local production of TNF-α and IL-6. The differentiation and activity of osteoclasts stimulated with AaLPS were diminished in the presence of BLT1 antagonist or 5-LO inhibitor, but not in the presence of cysteinyl leukotriene receptor antagonist. The osteoclast differentiation induced by PAF was impaired by the BLT1 antagonism. Conclusion In conclusion, LTB4 but not CysLTs is important for Aa-induced alveolar bone loss. Overall, LTB4 affects osteoclast differentiation and activity and is a key intermediate of PAF-induced osteoclastogenesis.

Made available in DSpace on 2018-12-11T17:23:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-09-28. Added 1 bitstream(s) on 2019-10-09T18:32:04Z : No. of bitstreams: 1 S1806-83242017000100263.pdf: 1804060 bytes, checksum: f801b86bddbefbfe6db39a9edbccd4ff (MD5) This study aimed to characterize the dynamics of suppressor of cytokine signaling (SOCS1) expression in a rat model of lipopolysaccharide-induced periodontitis. Wistar rats in the experimental groups were injected three times/week with LPS from Escherichia coli on the palatal aspect of the first molars, and control animals were injected with vehicle (phosphate-buffered saline). Animals were sacrificed 7, 15, and 30 days after the first injection to analyze inflammation (stereometric analysis), bone loss (macroscopic analysis), gene expression (qRT-PCR), and protein expression/activation (Western blotting). The severity of inflammation and bone loss associated with LPS-induced periodontitis increased from day 7 to day 15, and it was sustained through day 30. Significant (p < 0.05) increases in SOCS1, RANKL, OPG, and IFN-γ gene expression were observed in the experimental group versus the control group at day 15. SOCS1 protein expression and STAT1 and NF-κB activation were increased throughout the 30-day experimental period. Gingival tissues affected by experimental periodontitis express SOCS1, indicating that this protein may potentially downregulate signaling events involved in inflammatory reactions and bone loss and thus may play a relevant role in the development and progression of periodontal disease. Universidade Federal de Goiás - UFG, Faculty of Dentistry, Department of Periodontology, Goiânia, GO, Brazil Universidade Estadual Paulista - UNESP, School of Dentistry at Araraquara, Department of Diagnosis and Surgery, Araraquara, SP, Brazil Universidade Estadual Paulista - UNESP, School of Dentistry at Araraquara, Department of Physiology and Pathology, Araraquara, SP, Brazil Universidade de São Paulo - USP, School of Dentistry at Bauru, Department of Biological Sciences, Bauru, SP, Brazil

Alveolar bone loss is a result of an aggressive form of periodontal disease (PD) associated with Aggregatibacter actinomycetemcomitans (Aa) infection. PD is often observed with other systemic inflammatory conditions, including arthritis. Melanocortin peptides activate specific receptors to exert antiarthritic properties, avoiding excessing inflammation and modulating macrophage function. Recent work has indicated that melanocortin can control osteoclast development and function, but whether such protection takes place in infection-induced alveolar bone loss has not been investigated. The purpose of this study was to evaluate the role of melanocortin in Aa-induced PD. Mice were orally infected with Aa and treated with the melanocortin analog DTrp8-γMSH or vehicle daily for 30 d. Then, periodontal tissue was collected and analyzed. Aa-infected mice treated with DTrp8-γMSH presented decreased alveolar bone loss and a lower degree of neutrophil infiltration in the periodontium than vehicle-treated animals; these actions were associated with reduced periodontal levels of TNF-α, IFN-γ, and IL-17A. In vitro experiments with cells differentiated into osteoclasts showed that osteoclast formation and resorptive activity were attenuated after treatment with DTrp8-γMSH. Thus, melanocortin agonism could represent an innovative way to tame overexuberant inflammation and, at the same time, preserve bone physiology, as seen after Aa infection.-Madeira, M. F. M., Queiroz-Junior, C. M., Montero-Melendez, T., Werneck, S. M. C., Correa, J. D., Soriani, F. M., Garlet, G. P., Souza, D. G., Teixeira, M. M., Silva, T. A., Perretti, M. Melanocortin agonism as a viable strategy to control alveolar bone loss induced by oral infection.

It is extremely important to assess variations between the most used radiographs in dental practice, since minimum distortion on obtained images may change diagnosis, treatment plan, and prognosis for the patient. For this, the distance between the enamel-cementum junction and the alveolar bone crest was measured on conventional and digitized periapical, bitewing, and panoramic radiographs and compared among them. From a total of 1484 records, 39 sets of radiographs that fulfilled the inclusion criteria of the study sample were selected. The measurements were grouped according to the intensity of bone loss. Statistically significant difference was found in the averages of the measurements assessed in radiographs with absence of bone loss between conventional panoramic and periapical radiographs, between digitized panoramic and periapical radiographs and between digitized bitewing and panoramic radiographs. By analyzing the results of this work and considering the research protocol used, one can conclude that small losses in height of alveolar bone crest observed in panoramic radiographs should be cautiously evaluated, as they may be overestimated.

INTRODUCION: The quality of dental restorations can be directly related to the maintenance of periodontal health. Particularly in relation to the contour of interproximal restorations, radiographs allow the assessment of possible excess or lack of proximal contact of restorative materials.OBJECTIVE: To evaluate the frequency of adequate and inadequate restorations, the type of restorative material and the relationship of these parameters with periodontal alterations.METHODS: One hundred digital panoramic radiographs were evaluated, with interproximal restorations being observed on these examinations, classifying them according to the material used and the quality of interproximal restoration and the presence of periodontal alterations. Thepossible correlation between these parameters was evaluated.RESULTS: The frequency of adequate restorations was 48% of restored proximal surfaces. Among the inadequate restorations, 46.2% and 53.8% were over-contour and lack of proximal contact, respectively. The restorations were metallic in 64% of cases.CONCLUSIONS: Over-contour were more common among metal restorations and lack of proximal contact was more frequent among non-metal restorations. The presence of restorations was associated with increased prevalence of periodontal alterations. INTRODUÇÃO: A qualidade das restaurações dentárias pode estar diretamente relacionada à manutenção da saúde periodontal. Particularmente, em relação ao contorno das restaurações proximais, o exame radiográfico permite avaliar a ocorrência de excessos ou ausência de ponto de contato do material restaurador.OBJETIVO: Avaliar a qualidade das restaurações dentárias, o tipo de material restaurador e a relação dessas observações com alterações periodontais.MÉTODOS: Cem radiografias digitais panorâmicas foram avaliadas, com foco na observação das restaurações proximais, classificando-as de acordo com o material utilizado, a qualidade da restauração e a presença de alterações periodontais. Foi avaliada a possível correlação entre os parâmetros.RESULTADOS: A frequência de restaurações adequadas, nas superfícies proximais, foi de 48%. Ao se considerar o percentual de restaurações insatisfatórias, 46,2% e 53,8% apresentavam sobrecontorno e ausência de contato proximal, respectivamente. As restaurações eram metálicas em 64% dos casos.CONCLUSÃO: A ocorrência de sobrecontorno foi mais prevalente entre as restaurações metálicas e a ausência de contato proximal foi mais frequente quando da existência de restaurações em material não-metálico. A presença de restaurações proximais estava associada ao aumento de alterações periodontais.

Objective Soft tissues and buccal bone plate remodeling after immediate implantation in sockets with thin buccal bone, using the flapless approach with or without bone graft into the buccal gap, was compared between sites with thin and normal gingiva. Material and methods Eight dogs had the gingiva of one side of the mandible thinned, the mandibular premolars were extracted without flaps, and 4 implants were installed in each side, positioned 1.5 mm from the buccal bone. The sites were randomly assigned into: TG (test group) = thin gingiva; TG + GM (TG with grafting material); CG (control group) = normal gingiva; and CG + GM (CG with grafting material). Buccal bone thickness (BBT), thickness of keratinized tissue (TKT), alveolar thickness (AT), gingival recession (GR), and probing depth (PD) were clinically evaluated. Within 12 weeks the dogs were sacrificed and the samples were analyzed by micro-computerized tomography. Results A thin BBT was observed in all the dogs. The presurgical procedures reduced TKT in the test group, with minimal changes of the AT. There were no statistically significant differences among the groups for the clinical parameters and the tomographic analysis showed similar linear and tri-dimensional bone reduction in all the groups. Conclusion The thickness of the buccal bone was a fundamental factor in buccal bone plate resorption, even with flapless implantation. The decrease in gingival thickness or the addition of a biomaterial in the gap did not influence the results.

5-Lipoxygenase (5-LO) metabolites are important pro-inflammatory lipid mediators. However, much still remains to be understood about the role of such mediators in bone remodeling. This study aimed to investigate the effect of 5-LO metabolites, LTB4 and CysLTs, in a model of mechanical loading-induced bone remodeling. Strain-induced tooth movement and consequently alveolar bone resorption/apposition was achieved by using a coil spring placed on molar and attached to incisors of C57BL6 (wild-type-WT), 5-LO deficient mice (5-LO(-/-)) and mice treated with 5-LO inhibitor (zileuton-ZN) or with antagonist of CysLTs receptor (montelukast-MT). The amount of bone resorption and the number of osteoclasts were determined morphometrically. The expression of inflammatory and bone remodeling markers in periodontium was analyzed by qPCR. Osteoclast differentiation and TNF-α production were evaluated in vitro using RAW 264.7 cells treated with LTB4 or LTD4. Bone resorption, TRAP(+) cells and expression of Tnfa, Il10 and Runx2 were significantly diminished in 5-LO(-/-), ZN- and MT-treated mice. The expression of Rank was also reduced in 5-LO(-/-) and MT-treated mice. Accordingly, LTB4 and LTD4 in association with RANKL promoted osteoclast differentiation and increased TNF-α release in vitro. These data demonstrate that the absence of 5-LO metabolites, LTB4 and CysLTs reduces osteoclast recruitment and differentiation, consequently diminishing bone resorption induced by mechanical loading. Thus, 5-LO might be a potential target for controlling bone resorption in physiological and pathological conditions.

The aim of this study was to unravel the mechanisms by which interleukin (IL)-10, a potent pleiotropic cytokine, modulates alveolar bone homeostasis in C57BL/6 wild-type (WT) and IL-10 knockout (IL-10 KO) mice, evaluated at 8, 24, and 48 wk of age. Interleukin-10 KO mice presented significant alveolar bone loss when compared with WT mice, and this was not associated with changes in leukocyte counts or bacterial load. The levels of expression of messenger RNA (mRNA) for tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6, transforming growth factor-beta (TGF-beta), receptor activator of nuclear factor kappaB ligand (RANKL), osteoprotegerin (OPG), and matrix metalloproteinase 13 (MMP13) were similar between both strains, whereas a significant decrease of tissue inhibitor of metalloproteinase 1 (TIMP1) mRNA expression was found at 48 wk in IL-10 KO mice. The osteoblast markers core binding factor alpha1 (CBFA1) and type I collagen (COL-I) were expressed at similar levels in both strains, whereas the levels of alkaline phosphatase (ALP) and osteocalcin (OCN), and those of the osteocyte markers phosphate-regulating gene endopeptidases (PHEX) and dentin matrix protein 1 (DMP1) were significantly lower in IL-10 KO mice. Our results demonstrate that the alveolar bone loss in the absence of IL-10 was associated with a reduced expression of osteoblast and osteocyte markers, an effect independent of microbial, inflammatory or bone-resorptive pathways.