Imunoexpressão de fatores reguladores da osteoclastogênese na doença periodontal em humanos e sua relação com os parâmetros clínicos

Periodontal disease is an infection initiated by oral periodontal pathogens that trigger an immune response culminating in tissue destruction. This destruction is mediated by the host by inducing the production and activation of lytic enzymes, cytokines and the stimulation of osteoclastogenesis. The aim of this study was to compare the immunohistochemical expression of factors involved in bone resorption, RANKL (Ligand Receptor Activator of Nuclear Factor kappa B), OPG (Osteoprotegerin) and TNF-α (tumor necrosis factor alpha) between the gingival healthy, gingivitis and chronic periodontitis and correlate them with clinical parameters. The sample consisted of 83 cases and 12 clinically healthy gums, 42 gingivitis and 29 periodontitis, from 74 adolescent and adult patients with a mean age of 35 years, without systemic changes and non-smokers, predominantly female and race brown. There was no statistically significant difference for the expression of anti-RANKL (p = 0.581) and RANKL / OPG ratio (p = 0.334) when comparing the three conditions, but the anti-OPG and anti-TNF-α showed statistically significant between the types of injury (p = 0.001 and p <0.001, respectively), showing greatest expression in periodontitis. In cases of periodontitis, the variable clinical attachment loss (PIC) was statistically significant and positive correlation, respectively, with immunostaining of anti-RANKL (p = 0.002, p = 0.001 and r = 0.642), anti-OPG (p = 0.018, p = 0.014 and r = 0.451), anti-TNF-α (p = 0.032, p = 0.014 and r = 0.453) and the percentage ratio of RANKL / OPG (p = 0.018, p = 0.002 and r = 0.544). The tooth mobility (MB) showed a statistically significant difference only with immunohistochemical anti-RANKL (p = 0.026), and probing depth (PD) was positively correlated with anti-RANKL (p = 0.028 and r = 0.409), both in cases of periodontitis. Only in cases of gingivitis TNF-α was positively correlated with RANKL (p = 0.012 and r = 0.384) and the RANKL / OPG ratio (p = 0.027 and r = 0.341). Given these results, we conclude that the greatest expression of TNF-α in periodontitis demonstrates a relationship with the progression and severity of periodontal disease and the correlation between all antibodies and clinical attachment loss demonstrates their involvement in periodontal bone resorption

Treatment of Experimental Periodontal Disease by Photodynamic Therapy in Rats With Diabetes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Experimental periodontal disease treatment by subgingival irrigation with tetracycline hydrochloride in rats

Objective: The aim of this study was to compare subgingival irrigation with tetracycline hydrochloride (TTC-HCL) as adjunctive treatment to scaling and root planning (SRP) on induced periodontitis in rats. Material and Methods: In 60 rats, periodontal disease was ligature-induced at the mandibular left first molar. After 7 days, the ligature was removed and all animals were submitted to SRP, and divided into 2 groups according to the following treatment: C (n=30) - subgingival irrigation with 1 mL of saline; T (n=30) - subgingival irrigation with 1 mL of TTC-HCL (50 mg/mL). Ten animals in each group were euthanized at 7, 15 and 30 days posttreatment. The histometric values were statistically analyzed (p<0.05). Results: In the histometric analysis, at 7, 15 and 30 days, Group T (0.72+/-0.05 mm(2), 0.57+/-0.14 mm(2), 0.62+/-0.07 mm(2)), showed less bone loss (p<0.05) than Group C (1.35+/-0.25 mm(2); 1.40+/-0.31 mm(2); 1.29+/-0.27 mm(2)), respectively. Conclusions: Subgingival irrigation with TTC-HCL was an effective adjunctive treatment for periodontal disease induced in rats.

Smoking and Periodontal Disease: Clinical Evidence for an Association

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

The influence of loss of bone mass on induced periodontal disease: A radiographic and densitometric study of female rats

Background: Changes in mineral density in the mandibular and femoral bones (BMD) after estrogen deficiency caused by ovariectomy (OVX) and the influence of these changes on induced periodontal disease were evaluated in female rats.Methods: Forty-eight female Holtzman rats (90 days old) were randomly divided into five groups: 0: control (N = 9); 1: SHAM without induced periodontal disease (N = 11); 2: SHAM with induced disease (N = 10); 3: OVX without induced disease (N = 9); and 4: OVX with induced disease (N = 9). In groups 2 and 4, the first lower molars were tied with ligatures for 30 days 120 days after surgery. After 5 months the animals were sacrificed to measure global mineral density (BMD) and that of the sub-regions of the mandible and femur by dual energy x-ray absorptiometry (DXA). The extent of vertical bone loss was evaluated with digital radiography by measuring the distance from the bone crest to the cemento-enamel junction at the mesial of the first lower molar.Results: Results of the femur (Kruskal-Wallis test) showed a significant difference (P < 0.001) between the groups SHAM and OVX in bone density values for all regions. Comparison between the groups in relation to the BMD of the mandible, both in the sub-regions and global revealed no differences (P < 0.05). The vertical bone loss measured for the groups with induced disease was similar (P= 0.713).Conclusions: Differences between the groups were found in the bone mineral density BMD of the femur but not of the mandible. OVX had no influence on induced periodontal disease.

Potent anti-inflammatory effects of systemically administered curcumin modulate periodontal disease in vivo

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The Potential of p38 MAPK Inhibitors to Modulate Periodontal Infections

Periodontal disease initiation and progression occurs as a consequence of the host immune inflammatory response to oral pathogens. The innate and acquired immune systems are critical for the proper immune response. LPS, an outer membrane constituent of periodontal pathogenic bacteria, stimulates the production of inflammatory cytokines IL-1 beta TNF alpha IL-6 and RANKL either directly or indirectly. In LPS-stimulated cells, the induction of cytokine expression requires activation of several signaling pathways including the p38 MAPK pathway. This review will discuss the significance of the p38 MAPK pathway in periodontal disease progression and the potential therapeutic consequences of pharmacological antagonism of this pathway in the treatment of periodontal diseases.

Evaluation of partially dentate patients' knowledge about caries and periodontal disease

Objective: This investigation evaluated the knowledge of dental caries and periodontal disease among removable partial denture (RPD) wearers.Method: A total of 127 partially dentate patients participated in this observational study. A structured questionnaire, which included eight questions referring to knowledge about aetiology and prevention of dental caries and periodontal disease, was developed in the local language (Portuguese) and used to collect the data of all the partial denture wearers. A descriptive analysis of data was performed by means of drafting tables.Results: The results demonstrated that 68.5% of patients interviewed had previously received information about oral health care. With regard to bacterial plaque, it was observed that only 34.6% reported having knowledge of this. Whereas, in relation to caries, 76.4% of the interviewees replied that they knew the meaning of this. Nevertheless, 28.3% referred to caries as a whole in the teeth, 16.5% as bad teeth and 9.4% bacteria/creatures on the teeth. Only 17.3% of the partially edentulous patients evaluated were shown to know what disease of the gingiva was.Conclusion: By means of the methodology applied, it could be concluded that the patients who wore RPDs presented deficient knowledge with regard to the prevention, aetiology and development of dental caries and periodontal disease.

Periodontal conditions in a 7-19-year-old student population in Araraquara, São Paulo, Brazil, 1995

O objetivo deste estudo foi verificar as condições periodontais e necessidades de tratamento em crianças e adolescentes, com idades entre 7 e 19 anos, matriculados em Escolas Públicas de Araraquara, SP, Brasil, em 1995, com o propósito de se obter um banco de dados-base inicial para o monitoramento das mudanças no estado periodontal. Uma amostra de 1956 crianças e adolescentes foi examinada por duas examinadoras, previamente calibradas, usando o CPITN. Os resultados mostraram que o sangramento gengival foi a condição periodontal mais frequentemente observada em todas as idades, com média de 3,0 sextantes afetados na idade de 15 anos. A presença de cálculo dental aumentou com a idade. No grupo etário de 15-19 anos, o cálculo dental e as bolsas periodontais rasas (3,5-5,5 mm) foram observados em 39,8% e 1,6% dos adolescentes, respectivamente. Com o propósito de alcançar a meta da OMS de não mais do que um sextante com escores 1 (sangramento) ou 2 (presença de cálculo dental) do CPITN na idade de 15 anos, prioridade deve ser dada aos programas de prevenção primária para que a saúde periodontal da maioria seja beneficiada.

Periodontal changes in patients undergoing radiotherapy

Background: the purpose of this study was to evaluate changes in the periodontium in patients who received head and neck radiation therapy.Methods: Periodontal clinical parameters (probing depth, clinical attachment level, gingival recession, plaque index, and bleeding on probing) were assessed on 27 patients before and 6 to 8 months following radiation therapy in the head and neck area.Results: the greatest changes occurred in clinical attachment level: overall, 70.3% of the patients showed a loss, with 92% evincing loss in the mandible. Attachment loss was directly related to the field of radiation and was greater when the jaws were actually included in the irradiated area.Conclusion: Periodontal status should be evaluated prior to and following radiation therapy in the oral-maxillary-facial region to help ensure that periodontal health is maintained in oncology patients.

Alloxan-Induced Diabetes Triggers the Development of Periodontal Disease in Rats

Background. Periodontal disease in diabetic patients presents higher severity and prevalence; and increased severity of ligature-induced periodontal disease has been verified in diabetic rats. However, in absence of aggressive stimuli such as ligatures, the influence of diabetes on rat periodontal tissues is incompletely explored. The aim of this study was to evaluate the establishment and progression of periodontal diseases in rats only with diabetes induction. Methodology/Principal Findings. Diabetes was induced in Wistar rats (n = 25) by intravenous administration of alloxan (42 mg/kg) and were analyzed at 1, 3, 6, 9 and 12 months after diabetes induction. The hemimandibles were removed and submitted to radiographical and histopathological procedures. A significant reduction was observed in height of bone crest in diabetic animals at 3, 6, 9 and 12 months, which was associated with increased numbers of osteoclasts and inflammatory cells. The histopathological analyses of diabetic rats also showed a reduction in density of collagen fibers, fibroblasts and blood vessels. Severe caries were also detected in the diabetic group. Conclusions/Significance. The results demonstrate that diabetes induction triggers, or even co-induces the onset of alterations which are typical of periodontal diseases even in the absence of aggressive factors such as ligatures. Therefore, diabetes induction renders a previously resistant host into a susceptible phenotype, and hence diabetes can be considered a very important risk factor to the development of periodontal disease.

MKK3/6-p38 MAPK negatively regulates murine MMP-13 gene expression induced by IL-1 beta and TNF-alpha in immortalized periodontal ligament fibroblasts

Matrix metalloprotease-13 (MMP-13) or collagenase-3 is involved in a number of pathologic processes such as tumor metastasis and angiogenesis, osteoarthritis, rheumatoid arthritis and periodontal diseases. These conditions are associated with extensive degradation of both connective tissue and bone. This report examines gene regulation mechanisms and signal transduction pathways involved in Mmp-13 expression induced by proinflammatory cytokines in periodontal ligament (PDL) fibroblasts. Mmp-13 mRNA expression was increased 10.7 and 9.5 fold after stimulation with IL-1 beta (5 ng/mL) and TNF-alpha (10 ng/mL), respectively. However, inhibition of p38 MAPKinase with SB203580 resulted in significant (p < 0.001) induction (23.2 and 18.1 fold, respectively) of Mmp-13 mRNA as assessed by real time PCR. Negative regulation of IL-1 induced Mmp-13 expression was confirmed by inhibiting p38 MAPK gene expression with siRNA. Transient transfection of dominant negative forms of MKK3 and MKK6 also resulted in increased levels of Mmp-13 mRNA after IL-1 beta stimulation. Mmp-13 mRNA expression induced by TNF-alpha was decreased by JNK and ERK inhibition. Western blot and zymogram analysis indicated that Mmp-13 protein expression induced by the proinflammatory cytokines were also upregulated by inhibition of p38 MAPK. Reporter gene experiments using stable cell lines harboring 660-bp sequence of the murine Mmp-13 proximal promoter indicated that transcriptional mechanisms were at least partially involved in this negative regulation of Mmp-13 expression by p38 MAPK and upstream MKK3/6. These results suggest a negative transcriptional regulatory mechanism mediated by p38 MAPK and upstream MKK3/6 on Mmp-13 expression induced by proinflammatory cytokines in PDL fibroblasts. (c) 2005 Elsevier B.V./International Society of Matrix Biology. All rights reserved.

The relationship of oral malodor in patients with or without periodontal disease

Background: Halitosis has been correlated with the concentration of volatile sulfur compounds (VSC) produced in the oral cavity by metabolic activity of bacteria colonizing the periodontal area and the dorsum of the tongue. The aim of this study was to determine whether there is some relationship between the presence of N-benzoyl-DL-arginine-2-napthylamide (BANA)positive species Treponema denticola, Porphyromonas gingivalis, and Bacteroides forsythus and clinical and oral malodor parameters.Methods: Twenty-one subjects (21 to 59 years old) with probing depths (PD) >3.0 mm and 20 subjects (21 to 63 years old) with PD less than or equal to3.0 mm (controls) participated. The quality of the mouth air was assessed organoleptically, and a portable sulfide monitor was used to measure the concentration of VSC. Clinical parameters, plaque index (PI) and gingival index (GI), were obtained from 6 teeth. Samples for BANA test were taken from the dorsal surface of the tongue, saliva, and the 6 reference teeth.Results: the scores of PI, GI, subgingival samples that tested positive for BANA hydrolyzing species, organoleptic ratings, and VSC values were significantly higher in the subjects with PD >3.0 mm (P <0.01, Mann-Whitney U test). There was a correlation between BANA hydrolysis by subgingival plaque bacteria and VSC values (r = 0.55, P <0.01), and between GI and VSC values (r = 0.48, P <0.05) in patients with PD >3.0 mm. There was no significant correlation between these parameters in the control group.Conclusion: These results confirm that the BANA hydrolyzing bacteria in the subgingival plaque are an important source of malodor production in the oral cavity.

Influence of the period after ovariectomy on femoral and mandibular bone density and on induced periodontal disease

Background: This study investigated the influence of the period after ovariectomy on femoral and mandibular bone mineral density (BMD) and on induced periodontal disease.Methods: One hundred and twenty-six female Holtzman rats were divided into nine groups: control, sham surgery (SHAM) with and without induction of periodontal disease for 51 and 150 days, and ovariectomy (OVX) with and without induction of periodontal disease for 51 and 150 days. Periodontal disease was induced by placing ligatures on the first lower molars during the last 30 days of each period. BMD was measured by dual-energy x-ray absorptiometry. Vertical bone loss was determined by measuring the distance from the alveolar bone crest to the cemento-enamel junction on the mesial side of the first lower molar.Results: Statistical analyses (Kruskal-Wallis test) revealed a significant difference between the OVX and SHAM groups' global and femoral proximal epiphysis BMD (P < 0.001) for 150 days and in the global evaluation for 51 days. For mandibular BMD, no difference was found between the groups of each period. Influence of the period on femoral BMD was found only for the SHAM groups, with lower BMD for the 51-day period compared to the 150-day period (P < 0.05). In the global evaluation of the mandible, a lower BMD was found after 51 days. The period was a contributing factor for the vertical bone loss, and it resulted in higher values for the 51-day period (P < 0.05).Conclusion: the period influenced the femoral BMD and the vertical bone loss in induced periodontal disease.

Transcriptional activation of MMP-13 by periodontal pathogenic LPS requires p38 MAP kinase

Matrix metal loprotease-13 (MMP-13) is induced by pro-inflammatory cytokines and increased expression is associated with a number of pathological conditions such as tumor metastasis, osteoarthritis, rheumatoid arthritis and periodontal diseases. MMP-13 gene regulation and the signal transduction pathways activated in response to bacterial LPS are largely unknown. In these studies, the role of the mitogen-activated protein kinase (MAPK) pathways in the regulation of MMP-13 induced by lipopolysaccharide was investigated. Lipopolysaccharide from Escherichia coli and Actinobacillus actinomycetemcomitans significantly (P < 0.05) increased MMP-13 steady-state mRNA (average of 27% and 46% increase, respectively) in murine periodontal ligament fibroblasts. MMP-13 mRNA induction was significantly reduced by inhibition of p38 MAP kinase. Immunoblot analysis indicated that p38 signaling was required for LPS-induced MMP-13 expression. Lipopolysaccharide induced proximal promoter reporter (-660/+32 mMMP-13) gene activity required p38 signaling. Collectively, these results indicate that lipopolysaccharide-induced murine MMP-13 is regulated by p38 signaling through a transcriptional mechanism.