C. Rossa

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

AIMSnEvaluate the signaling pathways associated with inflammatory mediators activated in two models of experimental periodontitis.nnnMAIN METHODSnTwo models were used: lipopolysaccharide (LPS) injections and ligature placement. Wistar rats were used and 30 microg LPS from Escherichia coli was injected twice a week into the palatal aspect of the upper molars. Ligatures were placed around lower first molars. A control group received injections of PBS on the palatal gingivae whereas no ligatures were placed on the lower molars. Samples were collected 5, 15 and 30 days and processed for analysis by Western blotting and stereometry.nnnKEY FINDINGSnThe ligature model was associated with rapid and transient activation of extracellular-regulated kinases (ERK) and p38 mitogen-activated protein kinase (MAPK) as well as of nuclear factor kappa B (NF-kappaB). Activation of these signaling pathways on the LPS model was delayed but sustained throughout the 30-day experimental period. Inflammatory changes induced by both models were similar; however there was a significant reduction on inflammation degree on the ligature model, which paralleled the decrease observed on the activation of the signaling pathways. Activation of signal transducer and activator of transcription (STAT)-3 by phosphorylation of Tyrosine residues and of STAT-5 was observed only on the ligature model.nnnSIGNIFICANCEnRegulation of gene expression results from the activation of signaling pathways initiated by receptor-ligand binding of external antigens and also of cytokines produced by the host immune system. Understanding the signaling pathways relevant for a given condition may provide information useful for novel therapeutic approaches.

Simvastatin therapy in cyclosporine A-induced alveolar bone loss in rats

BACKGROUND AND OBJECTIVEnCyclosporine A treatment is important in the therapy of a number of medical conditions; however, alveolar bone loss is an important negative side-effect of this drug. As such, we evaluated whether concomitant administration of simvastatin would minimize cyclosporine A-associated alveolar bone loss in rats subjected, or not, to experimental periodontal disease.nnnMATERIAL AND METHODSnGroups of 10 rats each were treated with cyclosporine A (10 mg/kg/day), simvastatin (20 mg/kg/day), cyclosporine A and simvastatin concurrently (cyclosporine A/simvastatin) or vehicle for 30 days. Four other groups of 10 rats each received a cotton ligature around the lower first molar and were treated similarly with cyclosporine A, simvastatin, cyclosporine A/simvastatin or vehicle. Calcium (Ca(2+)), phosphorus and alkaline phosphatase levels were evaluated in serum. Expression levels of interleukin-1beta, prostaglandin E(2) and inducible nitric oxide synthase were evaluated in the gingivomucosal tissues. Bone volume and numbers of osteoblasts and osteoclasts were also analyzed.nnnRESULTSnTreatment with cyclosporine A in rats, with or without ligature, was associated with bone loss, represented by a lower bone volume and an increase in the number of osteoclasts. Treatment with cyclosporine A was associated with bone resorption, whereas simvastatin treatment improved cyclosporine A-associated alveolar bone loss in all parameters studied. In addition, simvastatin, in the presence of inflammation, can act as an anti-inflammatory agent.nnnCONCLUSIONnThis study shows that simvastatin therapy leads to a reversal of the cyclosporine A-induced bone loss, which may be mediated by downregulation of interleukin-1beta and prostaglandin E(2) production.

Differential regulation of MMP-13 expression in two models of experimentally induced periodontal disease in rats

OBJECTIVEnEvaluate expression of MMP-13 during the course of two models experimentally induced periodontal disease in rats.nnnDESIGNnExpression of MMP-13 at mRNA and protein levels was studied, respectively, by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Two experimental models were used: LPS injections and ligature placement. 30mug of LPS from Eschericia coli was injected twice a week into the palatal aspect of upper molars. Ligatures were placed at the gingival margin around lower first molars. Controls received injections of PBS vehicle and no ligatures on lower molars. Samples were collected 5, 15 and 30 days after initiation of periodontal disease and processed for extraction of total RNA, total protein, and routinely processed for histology.nnnRESULTSnBoth experimental models produced a significant increase on the inflammatory infiltrate that paralleled elevated levels of MMP-13 mRNA and protein at 5 and 15 days. The LPS model was associated with a sustained level of inflammation and increased MMP-13 mRNA throughout the 30 days, whereas the ligature model showed a decrease on the severity of inflammation and MMP-13 mRNA at the 30-day period. Interestingly, MMP-13 protein levels were diametrically contrary to the mRNA levels.nnnCONCLUSIONnMMP-13 expression during LPS- and ligature-induced experimental periodontal disease follows the increase on severity of inflammation at the earliest periods. At 30 days, there is a decrease on the severity of inflammation on the ligature model associated with decreased MMP-13 mRNA. There is a lack of transcription-translation coupling of MMP-13 gene in both experimental models.

Orthodontic movement of teeth with intraosseous defects: Histologic and histometric study in dogs

The purpose of this study was to evaluate histologically, in dogs, the periodontal healing of 1-walled intraosseous defects in teeth that were subjected to orthodontic movement toward the defects. The defects were surgically created bilaterally at the mesial aspects of the maxillary second premolars and distal aspects of the mandibular second premolars of 4 mongrel dogs. One week after creating the defects, an orthodontic appliance was installed, and the teeth were randomly assigned to 1 of 2 treatment groups: those in the test group received a titanium-molybdenum alloy rectangular wire spring that performed a controlled tipping root movement, and those in the control group received a passive stainless steel wire. Active orthodontic movement of the test teeth lasted 2 months and was followed by a stabilization period of another 2 months, after which the animals were killed. Throughout the study, routine daily plaque control was performed on the dogs with a topical application of a 2% chlorhexidine gel. The results showed no difference between the groups, with some regularization of the defects and periodontal regeneration limited to the apical portion of the defects. Histometric analysis showed a significant difference in bone height; on average, it was 0.53 mm smaller in the test group. It was concluded that orthodontic movement does not interfere with the healing of 1-walled intraosseous defects, with the exception of the linear extent of new bone apposition.