Expression of the Interleukin-10 Signaling Pathway Genes in Individuals With Down Syndrome and Periodontitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

MKK3/6-p38 MAPK signaling is required for IL-1 beta and TNF-alpha-induced RANKL expression in bone marrow stromal cells

Coupled bone turnover is directed by the expression of receptor-activated NF-kappa B ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Proinflammatory cytokines, such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) induce RANKL expression in bone marrow stromal cells. Here, we report that IL-1 beta and TNF-alpha-induced RANKL requires p38 mitogen-activating protein kinase (MAPK) pathway activation for maximal expression. Real-time PCR was used to assess the p38 contribution toward IL-1 beta and TNF-alpha-induced RANKL mRNA expression. Steady-state RANKL RNA levels were increased approximately 17-fold by IL-1 beta treatment and subsequently reduced similar to 70%-90% when p38 MAPK was inhibited with SB203580. RANKL mRNA stability data indicated that p38 MAPK did not alter the rate of mRNA decay in IL-1 beta-induced cells. Using a RANKL-luciferase cell line receptor containing a 120-kB segment of the 5' flanking region of the RANKL gene, reporter expression was stimulated 4-5-fold by IL-1 beta or TNF-alpha treatment. IL-1 beta-induced RANKL reporter expression was completely blocked with specific p38 inhibitors as well as dominant negative mutant constructs of MAPK kinase-3 and -6. In addition, blocking p38 signaling in bone marrow stromal cells partially inhibited IL-1 beta and TNF-alpha-induced osteoclastogenesis in vitro. Results from these studies indicate that p38 MAPK is a major signaling pathway involved in IL-1 beta and TNF-alpha-induced RANKL expression in bone marrow stromal cells.

Expression of suppressor of cytokine signaling 1 and 3 in ligature-induced periodontitis in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Biomechanical Evaluation of Platform Switching in Different Implant Protocols: Computed Tomography-Based Three-Dimensional Finite Element Analysis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Signaling pathways associated with the expression of inflammatory mediators activated during the course of two models of experimental periodontitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Clinical and radiographic changes around dental implants inserted in different levels in relation to the crestal bone, under different restoration protocols, in the dog model

Background: The aim of the present study was to evaluate clinical and radiographic changes that occur around dental implants inserted in different levels in relation to crestal bone under different restoration protocols.Methods: Thirty-six implants were inserted in the edentulous mandible of six mongrel dogs. Each implant was assigned to an experimental group according to the distance from the top of the implant to the crestal bone: Bone Level (at crestal bone level), Minus 1 (1 mm below crestal bone), or Minus 2 (2 mm below crestal bone). Each hemimandible was submitted to a restoration protocol: conventional (prosthesis was installed 120 days after implant placement, including 30 days with healing cap) or immediate (prosthesis was installed 24 hours after implant placement). Fixed partial prostheses were installed bilaterally in the same day. After 90 days, clinical and radiographic parameters were evaluated.Results: As long as the implants were inserted in more apical positions, the first bone-to-implant contact (fBIC) was positioned more apically (P<0.05). However, the apical positioning of the implants did not influence the ridge loss or the position of the soft tissue margin (PSTM) (P>0.05). In addition, in immediately restored sites, the PSTM was located significantly more coronally than that in conventionally restored sites (P=0.02).Conclusions: Despite the more apical positioning of the fBIC, the height of the peri-implant soft tissues and ridge was not jeopardized. Moreover, the immediate restoration protocol was beneficial to the maintenance of the PSTM. Further studies are suggested to evaluate the significance of these results in longer healing periods.

A dominant function of p38 mitogen-activated protein kinase signaling in receptor activator of nuclear factor-kappa B ligand expression and osteoclastogenesis induction by Aggregatibacter actinomycetemcomitans and Escherichia coli lipopolysaccharide

Background and Objective: Lipopolysaccharide from gram-negative bacteria is one of the microbial-associated molecular patterns that initiate the immune/inflammatory response, leading to the tissue destruction observed in periodontitis. The aim of this study was to evaluate the role of the p38 mitogen-activated protein kinase (MAPK) signaling pathway in lipopolysaccharide-induced receptor activator of nuclear factor-kappa B ligand (RANKL) expression by murine periodontal ligament cells.Material and Methods: Expression of RANKL and osteoprotegerin mRNA was studied by reverse transcription-polymerase chain reaction upon stimulation with lipopolysaccharide from Escherichia coli and Aggregatibacter actinomycetemcomitans. The biochemical inhibitor SB203580 was used to evaluate the contribution of the p38 MAPK signaling pathway to lipopolysaccharide-induced RANKL and osteoprotegerin expression. Stable cell lines expressing dominant-negative forms of MAPK kinase (MKK)-3 and MKK6 were generated to confirm the role of the p38 MAPK pathway. An osteoclastogenesis assay using a coculture model of the murine monocytic cell line RAW 264.7 was used to determine if osteoclast differentiation induced by lipopolysaccharide-stimulated periodontal ligament was correlated with RANKL expression.Results: Inhibiting p38 MAPK prior to lipopolysaccharide stimulation resulted in a significant decrease of RANKL mRNA expression. Osteoprotegerin mRNA expression was not affected by lipopolysaccharide or p38 MAPK. Lipopolysaccharide-stimulated periodontal ligament cells increased osteoclast differentiation, an effect that was completely blocked by osteoprotegerin and significantly decreased by inhibition of MKK3 and MKK6, upstream activators of p38 MAPK. Conditioned medium from murine periodontal ligament cultures did not increase osteoclast differentiation, indicating that periodontal ligament cells produced membrane-bound RANKL.Conclusion: Lipopolysaccharide resulted in a significant increase of RANKL in periodontal ligament cells. The p38 MAPK pathway is required for lipopolysaccharide-induced membrane-bound RANKL expression in these cells.

Tumor Necrosis Factor alpha and Interleukin-1 beta Modulate Calcium and Nitric Oxide Signaling in Mechanically Stimulated Osteocytes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Modulation of host cell signaling pathways as a therapeutic approach in periodontal disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Postoperative periodontal pain prevention using two dexamethasone medication protocols: A double-blind, parallel-group, placebo-controlled randomized clinical trial

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Kidney-Induced Hypertension Depends on Superoxide Signaling in the Rostral Ventrolateral Medulla

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Persistence of endodontic methacrylate-based cement residues on dentin adhesive surface treated with different chemical removal protocols

The aim of this study was to evaluate the persistence of methacrylate-based cement residues on the dentin, after dentin surface cleaning with ethanol or acetone, with or without previous application of a dentin adhesive. Forty bovine crown fragments were obtained and the dentin surface was washed with 1.0 mL of 2.5% sodium hypochlorite (NaOCl), followed by 0.1 mL of 17% ethylenediaminetetraacetic acid application for 3 min, and final irrigation with 2.5% NaOCl. The specimens were air dried and resin-based cement was rubbed onto the dentine surface with a microbrush applicator. In 20 specimens, previously to cement, a dentin adhesive was applied in all surfaces. After 15 min, the surface was scrubbed with a cotton pellet and moistened with ethanol or acetone, compounding the following groups: G199.5% ethanol and G2acetone, without previous use of dentin adhesive; G399.5% ethanol and G4acetone, with previous use of dentin adhesive. The dentin surface was scrubbed until the cement residues could not be visually detected. Sections were then processed for scanning electron microscopy and evaluated at 500x magnification and scores were attributed to each image according to the area covered by residual sealer, and data were subjected to KruskalWallis at 5% significance. The lower residue presence was observed in G3 (P = 0.005). All surface presented cement residues when acetone was used as cleaning solution (P = 0.0005). The cleaning solutions were unable to completely remove the cement residues from both surfaces. The ethanol used after previous application of the dentin adhesive promoted the lower presence of residues.

Persistence of resinous cement residues in dentin treated with different chemical removal protocols

The aim of this study was to evaluate the persistence of resin cement residues after dentin surface cleaning with different alcohol-based solutions or an essential oil (eucalyptol). Forty bovine teeth were sectioned in order to expose pulp chamber dentin to be washed with 1.0 mL of 2.5% sodium hypochlorite (NaOCl), followed by 0.1 mL of 17% EDTA application for 3 min, and final irrigation with 2.5% NaOCl. The specimens were air dried and resin-based cement was rubbed onto the dentine surface with a microbrush applicator. After 15 min, the surface was scrubbed with a cotton pellet and moistened with different dentin cleaning solutions, compounding the following groups: G195% ethanol, G270% ethanol, G370% isopropyl alcohol, or G4eucalyptol. The dentin was scrubbed until the cement residues could not be visually detected. Sections were then processed for SEM and evaluated at x 500 magnification. Scores were attributed to each image according to the area covered by residual sealer, and data were subjected to KruskalWallis at 5% significance. Eucalyptol promoted the most adequate dentin cleaning, although no statistical difference was detected amongst the groups (P > 0.05), except between the eucalyptol and 70% ethanol groups (P < 0.05). All the evaluated dentin cleaning solutions were unable to completely remove the cement residues from the dentin surface. Microsc. Res. Tech., 2012. (C) 2012 Wiley Periodicals, Inc.