Circulating matrix metalloproteinase-8 (MMP-8) and MMP-9 are increased in chronic periodontal disease and decrease after non-surgical periodontal therapy

Background: Periodontal disease shares risk factors with cardiovascular diseases and other systemic inflammatory diseases. The present study was designed to assess the circulating matrix metalloproteinases (MMPs) from chronic periodontal disease patients and, subsequently, after periodontal therapy. Methods: We compared the plasma concentrations of MMP-2. MMP-3, MMP-8, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2, and total gelatinolytic activity in patients with periodontal disease (n =28) with those of control subjects (n = 22) before and 3 months after non-surgical periodontal therapy. Results: Higher plasma MMP-3, MMP-8, and MMP-9 concentrations were found in periodontal disease patients compared with healthy controls (all P<0.05), whereas MMP-2, TIMP-1, and TIMP-2 levels were not different. Treatment decreased plasma MMP-8 and MMP-9 concentrations by 35% and 39%, respectively (both P<0.02), while no changes were found in controls. MMP-2, MMP-3, TIMP-1, and TIMP-2 remained unaltered in both groups. Plasma gelatinolytic activity was higher in periodontal disease patients compared with controls (P<0.001) and decreased after periodontal therapy (P<0.05). Conclusions: This study showed increased circulating MMP-8 and MMP-9 levels and proteolytic activity in periodontal disease patients that decrease after periodontal therapy. The effects of periodontal therapy suggest that it may attenuate inflammatory chronic diseases. (C) 2009 Published by Elsevier B.V.

Circulating Interleukin-6 and High-Sensitivity C-Reactive Protein Decrease After Periodontal Therapy in Otherwise Healthy Subjects

Background: Periodontal disease has been associated with many chronic inflammatory systemic diseases, and a common chronic inflammation pathway has been suggested for these conditions. However, few studies have evaluated whether periodontal disease, in the absence of other known inflammatory conditions and smoking, affects circulating markers of chronic inflammation. This study compared chronic inflammation markers in control individuals and patients with periodontal disease and observed whether non-surgical periodontal therapy affected inflammatory disease markers after 3 months. Methods: Plasma and serum of 20 controls and 25 patients with periodontal disease were obtained prior to and 3 months after non-surgical periodontal therapy. All patients were non-smokers, they did not use any medication, and they had no history or detectable signs and symptoms of systemic diseases. Periodontal and systemic parameters included probing depth, bleeding on probing, clinical attachment level, hematologic parameters, as well as the following inflammatory markers: interleukin (IL)-6, high-sensitivity C-reactive protein (hs-CRP), CD40 ligand, monocyte chemoattractant protein (MCP)-1, soluble P-selectin (sP-selectin), soluble vascular adhesion molecule (sVCAM)-1, and soluble intercellular adhesion molecule (sICAM)-1. Results: There were no differences in the hematologic parameters of the patients in the control and periodontal disease groups. Among the tested inflammatory markers, IL-6 concentrations were higher in the periodontal disease group at baseline compared to the controls (P=0.006). Therapy was highly effective (P<0.001 for all the analyzed clinical parameters), and a decrease in circulating IL-6 and hs-CRP concentrations was observed 3 months after therapy (P=0.001 and P=0.006, respectively). Our results also suggest that the CD40 ligand marker may have been different in the control and periodontal disease groups prior to the therapy (P=0.009). Conclusions: In apparently otherwise healthy patients, periodontal disease is associated with increased circulating concentrations of IL-6 and hs-CRP, which decreased 3 months after non-surgical periodontal therapy. With regard to the CD40 ligand, MCP-1, sP-selectin, sVCAM-1, and sICAM-1, no changes were seen in the periodontal disease group between baseline and 3 months after therapy. J Periodontol 2009;80:594-602.

Nonsurgical Periodontal Therapy Combined with Laser and Photodynamic Therapies for Periodontal Disease in Immunosuppressed Rats

Background. Periodontal disease is often associated with systemic diseases and is characterized by destruction of the tissues supporting the teeth. Patients using immunosuppressive drugs such as tacrolimus are among those who suffer from tissue destruction. Objective. We sought to evaluate the effects of laser and photodynamic therapies (PDT; nonsurgical) as an adjunct to scaling and rootplaning (SRP) in the treatment of corona-induced periodontitis in rats immunosuppressed with tacrolimus (Prograf). Materials and Methods. The animals were divided into 5 groups. Each groups had 6 rats. Group I, the control group, received only saline solution throughout the study period of 42 days and did not receive periodontal treatment; group II received saline solution and SRP; group III received tacrolimus (1 mg/kg per day) and was treated with SRP; group IV animals were treated identically to group III and then administered laser treatment; and in group V, the animals were treated identically to group III and then administered PDT. Results. Statistical analysis indicated decreased bone loss with the progression of time (P = .035). There was no difference between the bone loss associated with the types of treatment administered to groups I, II, and III (P > .9) or groups IV and V (P > .6). The analysis also indicated that immunosuppression was not a bone loss-determining factor. Conclusion. Laser and PDT therapies were effective as an adjunctive treatment to SRP in reducing bone loss caused by experimental periodontitis induced in animals being treated systemically with tacrolimus.

Effects of periodontal therapy on glycemic control and inflammatory markers

Background: Periodontitis, a complication of diabetes mellitus (DM), can induce or perpetuate systemic conditions. This double-masked, placebo-controlled study evaluated the effects of periodontal therapy (scaling and root planing [SRP]) on the serum levels of glycated hemoglobin (HbA1c) and on inflammatory biomarkers. Methods: Thirty subjects with type 2 DM and periodontitis were treated with SRP + placebo (SRP; N = 15) or with SRP + doxycycline (SRP+Doxy; N = 15), 100 mg/day, for 14 days. Clinical and laboratory data were recorded at baseline and at 3 months after treatment. Results: After 3 months, the reduction in probing depth Was 0.8 mm for the SRP group (P <0.01) and 1.1 mm for the SRP+Doxy group (P <0.01) followed by a 0.9% (SRP; P = 0.17) and 1.5% (SRP+Doxy; P<0.01) reduction in HbA1c levels. A significant reduction in interleukin (IL)-6; interferon-inducible protein 10; soluble fas ligand; granulocyte colony-stimulating factor; RANTES; and IL-12 p70 serum levels were also verified (N = 30). To our knowledge, this is the first report on the effects of periodontal therapy on multiple systemic inflammatory markers in DM. Conclusions: Periodontal therapy may influence the systemic conditions of patients with type 2 DM, but no statistical difference was observed with the adjunctive systemic doxycycline therapy. Moreover, it is possible that the observed improvement in glycemic control and in the reduction of inflammatory markers could also be due to diet, which was not controlled in our study. Therefore, a confirmatory study with a larger sample size and controlled diet is necessary.

Gingival crevicular fluid levels of MMP-8, MMP-9, TIMP-2, and MPO decrease after periodontal therapy

P>Background This study aimed at comparing the levels of matrix metalloproteinase (MMP)-8, tissue Inhibitor of MMPs (TIMP)-1 and TIMP-2, Myeloperoxidase (MPO), and MMP-9 in the gingival crevicular fluid (GCF) of chronic periodontitis (CP) patients and controls at baseline and 3 months after non-surgical therapy. Materials and Methods GCF was collected from one site of 15 control subjects and 27 CP patients. MMP-8, MMP-9, TIMP-1, and TIMP-2 were determined by Enzyme-linked immunoabsorbent assay; different forms of MMP-9, by gelatin zymography; and MPO, colorimetrically. Results At baseline, higher levels of MMP-8, TIMP-2, MPO, and the 87 kDa-MMP-9 were found in patients compared with controls (p < 0.001), and these molecules decreased after therapy (p < 0.03). There were no differences between the groups with respect to the higher molecular forms of MMP-9 (180, 130, 92 kDa) or total MMP-9 at baseline. No differences were observed in TIMP-1 levels. In controls, decreased levels of TIMP-2 and the higher molecular forms of MMP-9 (180, 130, 92 kDa) were found 3 months after therapy compared with baseline (p < 0.01). Conclusions Higher levels of MMP-8, TIMP-2, MPO, and 87 kDa MMP-9 were found in the GCF of patients compared with controls, and these markers decreased 3 months after periodontal therapy.

The role of obesity as a modifying factor in patients undergoing non-surgical periodontal therapy

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Nonsurgical Periodontal Therapy Combined with Laser and Photodynamic Therapies for Periodontal Disease in Immunosuppressed Rats

Background. Periodontal disease is often associated with systemic diseases and is characterized by destruction of the tissues supporting the teeth. Patients using immunosuppressive drugs such as tacrolimus are among those who suffer from tissue destruction. Objective. We sought to evaluate the effects of laser and photodynamic therapies (PDT; nonsurgical) as an adjunct to scaling and rootplaning (SRP) in the treatment of corona-induced periodontitis in rats immunosuppressed with tacrolimus (Prograf).Materials and Methods. The animals were divided into 5 groups. Each groups had 6 rats. Group I, the control group, received only saline solution throughout the study period of 42 days and did not receive periodontal treatment; group II received saline solution and SRP; group III received tacrolimus (1 mg/kg per day) and was treated with SRP; group IV animals were treated identically to group III and then administered laser treatment; and in group V, the animals were treated identically to group III and then administered PDT.Results. Statistical analysis indicated decreased bone loss with the progression of time (P = .035). There was no difference between the bone loss associated with the types of treatment administered to groups I, II, and III (P > .9) or groups IV and V (P > .6). The analysis also indicated that immunosuppression was not a bone loss-determining factor.Conclusion. Laser and PDT therapies were effective as an adjunctive treatment to SRP in reducing bone loss caused by experimental periodontitis induced in animals being treated systemically with tacrolimus.

The effect of non-surgical periodontal therapy on peroxidase activity in diabetic patients: a case-control pilot study

Objective: To evaluate the effect of periodontal therapy on clinical parameters as well as on total salivary peroxidase (TSP) activity and myeloperoxidase (MPO) activity in the gingival crevicular fluid (GCF) of patients with type 2 diabetes mellitus (DM2) and of systemically healthy individuals.Material and Methods: Twenty DM2 subjects with inadequate metabolic control (test group) and 20 systemically healthy individuals (control group), both groups with chronic periodontitis, were enrolled. Periodontal clinical parameters, namely periodontal probing depth (PD), clinical attachment level (CAL), visible plaque index (VPI), bleeding on probing (BOP), gingival bleeding index (GBI) and presence of suppuration (SUP), as well as TSP activity and GCF MPO activity, were assessed before and 3 months after non-surgical periodontal therapy.Results: At baseline and 3 months post-treatment, the test group presented a higher percentage of sites with VPI and BOP (p < 0.01). MPO activity in the GCF presented lower values (p < 0.05) for the test group at both baseline and the post-treatment period. The periodontal treatment resulted in a significant improvement of most clinical and enzymatic parameters for both groups (p < 0.05).Conclusions: In both groups, the periodontal therapy was effective in improving most clinical parameters and in reducing salivary and GCF enzymatic activity. The diabetic individuals presented lower MPO activity in the GCF.

Compliance with supportive periodontal therapy and its relation to the bleeding index

THIS IS A RETROSPECTIVE STUDY of 418 patients who received active periodontal treatment between the years of 1984 and 1990. The patients were instructed to return for supportive periodontal treatment (SPT) at 3 to 6-month intervals. The objective of this study was to evaluate patient compliance with periodic recall visits, and to study the relationship of bleeding upon probing in those who returned regularly. The patients were divided into 3 groups: patients who returned periodically for supportive treatment, patients who interrupted the proposed maintenance treatment, and patients who never returned after active periodontal treatment. Analysis was made for each group to correlate the degree of compliance with gender, disease classification, and type of treatment received. To analyze bleeding upon probing, 2 groups of patients were selected: a test group with 39 patients who had attended at least 10 recall visits and participated in the study for more than 40 months, and a control group of 21 patients who interrupted the SPT for at least 12 months. The results showed that 26% of the treated patients returned for SPT and, of those, 40% returned irregularly. There was a statistical significant difference in compliance in relation to disease classification and the type of treatment received, but no correlation was found between compliance and gender. There was a statistically significant difference in compliance between the test group and the control group in relation to the variation of the bleeding index.

Combination of orthodontic movement and periodontal therapy for full root coverage in a miller class iii recession: A case report with 12 years of follow-up

One of the main purposes of mucogingival therapy is to obtain full root coverage. Several treatment modalities have been developed, but few techniques can provide complete root coverage in a class III Miller recession. Thus, the aim of this case report is to present a successful clinical case of a Miller class III gingival recession in which complete root coverage was obtained by means of a multidisciplinary approach. A 17-year-old Caucasian female was referred for treatment of a gingival recession on the mandibular left central incisor. The following procedures were planned for root coverage in this case: free gingival graft, orthodontic movement by means of alignment and leveling and coronally advanced flap (CAF). The case has been followed up for 12 years and the patient presents no recession, no abnormal probing depth and no bleeding on probing, with a wide attached gingiva band. A compromised tooth with poor prognosis, which would be indicated for extraction, can be treated by orthodontic movement and periodontal therapy, with possibility of 100% root coverage in some class III recessions.

Interleukin 4 haplotypes of susceptibility to chronic periodontitis are associated with IL-4 protein levels but not with clinical outcomes of periodontal therapy

Different IL4 haplotypes were associated to susceptibility to/or protection against chronic periodontitis (CP). The aim of this study was to investigate if individuals carrying different haplotypes would present differences in clinical periodontal parameters and in the IL-4 levels at baseline, 45 and 90 days after non-surgical periodontal therapy. 62 patients were subdivided: genetically protected without CP (PH), genetically protected with CP (PCP), genetically susceptible with CP (SCP), genetically susceptible without CP (healthy) (SH). Clinical examination and gingival crevicular fluid (GCF) collection were performed for all patients, and IL-4 levels were measured by ELISA. At baseline, higher values for plaque index (PI, p = 0.013), gingival index (GI, p = 0.005) were observed for the SCP group in comparison to the PCP group but not after the completion of periodontal therapy. 45 and 90 days after the non-surgical therapy, PCP demonstrated significantly higher IL-4 levels than the SCP (p = 0.000002). Correlation analysis showed different results between clinical parameters and IL-4 production or GCF volume for groups with different genetic loads. The IL4 gene which was previously associated with susceptibility to CP was related with differences in the IL-4 protein levels in the GCF. However, independent of genetic carriage, individuals responded similarly to this therapy. © 2013 American Society for Histocompatibility and Immunogenetics.

Periodontopathogens levels and clinical response to periodontal therapy in individuals with the interleukin-4 haplotype associated with susceptibility to chronic periodontitis

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

Clinical outcomes of periodontal therapy are not influenced by the ATC/TTC haplotype in the IL8 gene

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

Haplotypes of susceptibility to chronic periodontitis do not influence MMP-8 levels or the outcome of non-surgical periodontal therapy

Introduction: Chronic periodontitis (CP) is a multifactorial condition, presenting immunoinflammatory reaction, in which a myriad of molecules including cytokines and matrix metalloproteinases (MMPs) interplays, making the system extremely intricate. There is scarce information regarding interconnections of biological influence among IL-4, IL-8 and MMP-8, mainly considering genetic polymorphisms, and also, whether this can influence the outcome of periodontal therapy. Previously, we reported that variants in the interleukin 4 (IL4) and interleukin 8 (IL8) genes were associated with CP in Brazilians. The aim of this study was to investigate, in individuals with different genetic backgrounds with regard to the IL4 or IL8 haplotypes, differences in the immunological levels of MMP-8 in gingival crevicular fluid (GCF) before and after non-surgical periodontal treatment. A total of 141 patients participated of this study, classified as susceptible or not to CP, according to the presence of haplotypes formed by polymorphysms in the IL4 or IL8 genes. All individuals received non-surgical periodontal therapy and follow–up continued for 45 days. The GCF samples were collected at baseline and on the 45th day. The MMP-8 levels were determined by ELISA. Results: No association was found between genetic backgrounds and MMP-8 levels in GCF or the outcome of non-surgical periodontal therapy. Conclusions: In this longitudinal clinical study, the presence of IL4 or IL8 haplotypes previously associated with CP did not influence the outcome of non-surgical periodontal therapy and the MMP-8 levels in the GCF. Additional studies are necessary to determine the mechanisms by which the IL4 or IL8 haplotypes affect individual susceptibility to CP.