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Journal of Periodontology | 2009

Interleukin-17, RANKL, and Osteoprotegerin Levels in Gingival Crevicular Fluid From Smoking and Non-Smoking Patients With Chronic Periodontitis During Initial Periodontal Treatment

Nurcan Buduneli; Eralp Buduneli; Necil Kutukculer

BACKGROUND This study was performed to evaluate the effects of initial periodontal treatment on the gingival crevicular fluid (GCF) levels of interleukin (IL)-17, soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), and osteoprotegerin (OPG) in smoking and non-smoking patients with chronic periodontitis. METHODS At baseline, GCF samples were obtained from 10 smoking and 10 non-smoking systemically healthy patients with chronic periodontitis. Initial periodontal treatment, consisting of motivation and instruction for daily plaque control and scaling and root planing (SRP), was performed. GCF sampling and clinical periodontal measurements were repeated 4 weeks after completion of SRP. The data were tested statistically by the Student t and Wilcoxon matched-pairs test and Spearman correlation analysis. RESULTS All clinical periodontal measurements had decreased significantly 4 weeks after SRP (P <0.001). GCF volume and the total amount and concentration of OPG decreased in smokers and non-smokers after SRP, whereas the IL-17 concentration increased (P <0.05). sRANKL levels did not differ between groups or with SRP (P >0.05). Significant correlations were found between baseline IL-17 and receptor activator of nuclear factor-kappa B ligand (RANKL) levels and between baseline papilla bleeding index and OPG levels (P <0.001 and P <0.05, respectively). CONCLUSIONS Neither smoking nor periodontal inflammation seemed to influence GCF RANKL levels in systemically healthy patients with chronic periodontitis. Smoking and non-smoking patients with chronic periodontitis were not affected differently by the initial periodontal treatment with regard to GCF IL-17 and OPG concentrations.


Journal of Periodontology | 2007

Matrix Metalloproteinases, Tissue Inhibitor of Matrix Metalloproteinase-1, and Laminin-5 γ2 Chain Immunolocalization in Gingival Tissue of Endotoxin-Induced Periodontitis in Rats: Effects of Low-Dose Doxycycline and Alendronate

Eralp Buduneli; Saynur Vardar-Şengül; Nurcan Buduneli; Gül Atilla; Jaana Wahlgren; Timo Sorsa

BACKGROUND Matrix metalloproteinases (MMPs) play important roles in tissue destruction mechanisms of periodontitis. MMP-8 and -13 are the major collagenases that act in extracellular matrix degradation in periodontal tissues. MMP-14 is a membrane-type MMP, and laminin (Ln)-- is a basal membrane component. The aim of the present study was to evaluate the effects of doxycycline and alendronate on gingival tissue expression of MMP-8, -13, and -14; tissue inhibitors of MMP (TIMP)-1; and Ln-5 γ2 chain in experimental periodontitis induced by Escherichia coli endotoxin (LPS) in rats. METHODS Experimental periodontitis was induced by repeated injection of LPS. Forty-four adult male Sprague-Dawley rats were divided into five study groups: saline control, LPS, LPS + doxycycline, LPS + alendronate, and LPS + doxycycline + alendronate. Doxycycline and alendronate were given as a single agent or as combination therapy during the 7 days of the experimental study period. On day 7, the rats were sacrificed, and the gingival tissues were analyzed immunohistochemically for expression of MMP-8, -13, and -14, Ln-- γ2 chain, and TIMP-1. Alveolar bone loss was evaluated morphometrically under a stereomicroscope. Data were tested statistically by Kruskal-Wallis and Mann-Whitney tests and Spearman correlation analysis. RESULTS Alveolar bone loss was significantly higher in the LPS, doxycycline, alendronate, and combination groups than in the saline control group (all P <0.01). MMP-8 expression was significantly higher in the LPS group than in the saline control group (P = 0.001). Individual administration of doxycycline or alendronate significantly decreased the expression of MMP-8 compared to LPS (P = 0.01). Combined drug administration reduced MMP-14 significantly compared to doxycycline (P = 0.004). No significant differences in Ln-5 γ2 chain expression were found between the study groups (P >0.05). MMP-14 significantly correlated with the Ln-5 γ2 chain in the LPS + alendronate group (P = 0.04) and with the amount of alveolar bone loss in the LPS + doxycycline + alendronate group (P = 0.03). CONCLUSIONS Our findings suggest that alendronate and/or doxycycline may inhibit MMP-8 expression significantly; particularly, their combined administration may provide beneficial effects in periodontal treatment. Moreover, individual administration of alendronate and doxycycline results in significant increases in TIMP-1 expression in gingiva. However, these effects of combined low-dose doxycycline and alendronate on MMPs and TIMP should be verified by clinical human trials before these agents are used in dental practice.


Journal of Periodontology | 2013

Gingival crevicular fluid, serum levels of receptor activator of nuclear factor-κB ligand, osteoprotegerin, and interleukin-17 in patients with rheumatoid arthritis and osteoporosis and with periodontal disease.

Pınar Gümüş; Eralp Buduneli; Başak Bıyıkoğlu; Kenan Aksu; Fulden Sarac; Christopher J. Nile; David F. Lappin; Nurcan Buduneli

BACKGROUND This study is performed to evaluate gingival crevicular fluid (GCF) and serum levels of soluble receptor activator of nuclear factor-κB ligand (sRANKL), interleukin (IL)-17A, IL-17E, IL-17F, IL-17A/F, and osteoprotegerin (OPG) in women with rheumatoid arthritis (RA), osteoporosis (OPR), and those who are systemically healthy (SH), all with periodontal disease. METHODS GCF and serum samples were obtained before any periodontal intervention from 17 women with RA, 19 with OPR, and 13 who were SH with periodontitis. Full-mouth clinical periodontal measurements were recorded. sRANKL, OPG, and IL-17 levels were determined by enzyme-linked immunosorbent assay. RESULTS Clinical periodontal measurements were similar in the three study groups. Although the total amounts of GCF albumin, OPG, IL-17A, and IL-17A/F were similar in the study groups, there were statistically significant differences in GCF concentrations of sRANKL, OPG, IL-17A, IL-17E, IL-17F, and IL-17A/F. The sRANKL/OPG ratios were significantly higher in the RA group than in the OPR and SH groups (P <0.05). Serum sRANKL, sRANKL/OPG, and IL-17A/IL-17E ratios were significantly higher, whereas OPG concentrations were significantly lower in the RA group compared to other groups (P <0.05). Serum IL-17A concentrations were significantly higher in the RA and OPR groups than in the SH group (P <0.05). CONCLUSION Increased inflammatory mediator levels in patients with RA, despite the long-term use of various anti-inflammatory drugs, suggest that these patients may have a propensity to overproduce these inflammatory mediators.


Journal of Periodontology | 2006

Dietary Supplementation of Omega-3 Fatty Acid and Circulating Levels of Interleukin-1β, Osteocalcin, and C-Reactive Protein in Rats

Saynur Vardar-Sengul; Nurcan Buduneli; Eralp Buduneli; Levent Kardeşler; Haluk Baylas; Gül Atilla; David F. Lappin; Denis F. Kinane

BACKGROUND In this study, we evaluated the effects of two different regimes of dietary supplementation of omega-3 fatty acid on serum levels of interleukin-1 beta (IL-1β), osteocalcin (OC), and C-reactive protein (CRP) in experimental periodontitis. METHODS Experimental periodontitis was induced by repeated injections of Escherichia coli lipopolysaccharide (LPS). Thirty-nine adult male Sprague-Dawley rats were divided into four study groups as follows: an LPS positive control group; a saline (negative) control group; and two different groups with omega-3 fatty acid dietary supplementation, one in which we gave the supplement subsequent to disease induction (TO3) and the other in which the agent was started prior to and continued subsequent to LPS injections (P + TO3). In the TO3 group, omega-3 fatty acid administration was performed for 14 days following induction of experimental periodontitis. In the P + TO3 group, omega-3 fatty acid was given for 14 days prior to the start of LPS injections and was continued for another 14 days subsequent to the induction of experimental periodontitis. On day 15 of the first LPS injection, serum samples were obtained and rats were sacrificed. Serum samples were analyzed for IL-1β, OC, and CRP concentrations by enzyme-linked immunosorbent assay. Defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by non-parametric tests. RESULTS LPS injection resulted in statistically significantly more bone loss compared to the saline control group (P <0.05). None of the omega-3 fatty acid administration groups showed evidence that this fatty acid was effective in preventing LPS-induced alveolar bone loss. TO3 and P + TO3 groups revealed significantly higher IL-1β and OC levels than the LPS group (P <0.05). The study groups exhibited no significant differences in the serum CRP levels. CONCLUSIONS Omega-3 fatty acid administration does not seem to influence circulating levels of CRP. The significantly increased serum OC level observed in both omega-3 fatty acid regimes is curious and could have an effect on bone turnover, as could the further significant increase in serum IL-1β, which could counteract any osteoblastic induction by OC through promotion of osteoclast activity. The lack of a therapeutic benefit of omega-3 fatty acid in this study, despite the effects on OC and IL-1β, is difficult to explain, and further studies are required to more fully assess the potential role of this fatty acid in periodontal treatment.


Journal of Periodontal Research | 2014

Is obesity a possible modifier of periodontal disease as a chronic inflammatory process? A case-control study.

Nurcan Buduneli; Başak Bıyıkoğlu; Tunç İlgenli; Eralp Buduneli; Ayse Nalbantsoy; Fulden Sarac; Denis F. Kinane

BACKGROUND AND OBJECTIVE This cross-sectional case-control study was conducted to provide a comparative evaluation of clinical periodontal measurements, together with serum levels of certain bioactive peptides and inflammatory cytokines, in relation to obesity. For this purpose, clinical periodontal measurements and the levels of serum leptin, adiponectin, interleukin-6 (IL-6), C-reactive protein and soluble intercellular adhesion molecule-1 of obese female individuals and their nonobese counterparts were compared. MATERIAL AND METHODS Sixty obese (body mass index (BMI) > 30) and 31 nonobese (BMI < 30) female subjects were recruited for the present study. Before any periodontal intervention, serum samples were obtained and full-mouth clinical periodontal measurements were recorded at six sites per tooth. ELISA was used for the biochemical analysis. Data were tested statistically. RESULTS Clinical attachment level was significantly higher in the obese group compared with the nonobese control group (p < 0.05). Serum levels of leptin and IL-6 were significantly higher in the obese group (p < 0.05). BMI correlated with the serum levels of inflammatory molecules (p < 0.05), but not with clinical periodontal parameters, in the obese group. CONCLUSION In conclusion, obesity does not seem to have a prominent effect on clinical periodontal parameters but it does have many correlations with circulating inflammatory molecules. As suggested in the literature, increased levels of leptin and IL-6 in the obese group might be one explanation for a possible relationship between obesity and periodontal disease. A prospective study is warranted to clarify, in greater detail, the effects of obesity on periodontal health.


Australian Dental Journal | 2010

Gingival status, crevicular fluid tissue-type plasminogen activator, plasminogen activator inhibitor-2 levels in pregnancy versus post-partum.

Nurcan Buduneli; S Becerik; Eralp Buduneli; Haluk Baylas; B Kinnby

BACKGROUND This study was conducted to evaluate a possible link between periodontal status of pregnant women and the plasminogen activator system in gingival crevicular fluid (GCF). METHODS GCF samples were obtained from four interproximal sites of anterior teeth in 43 women during the second trimester and also after delivery. Full mouth dental plaque, bleeding on probing (BOP) and probing depth (PD) values were recorded at six sites/tooth in each subject. GCF levels of tissue type plasminogen activator (t-PA) and its inhibitor, plasminogen activator-inhibitor-2 (PAI-2) were determined by ELISA. Data comparisons between pregnancy and post-partum were made by Wilcoxon signed rank test. RESULTS The number of pockets with a PD>4 mm and total volume of GCF sampled were reduced significantly after delivery (p=0.000 and p=0.013, respectively). No significant differences were detected in GCF concentrations of t-PA or PAI-2 between pregnancy and post-partum. CONCLUSIONS Our results suggest that GCF t-PA and PAI-2 concentrations are not affected by pregnancy. Reductions in PD values and GCF volume following delivery indicate a resolution of oedema in gingival tissues, possibly related to hormonal changes due to the ending of pregnancy.


Expert Opinion on Pharmacotherapy | 2010

Clinical findings and gingival crevicular fluid prostaglandin E2 and interleukin-1-beta levels following initial periodontal treatment and short-term meloxicam administration

Nurcan Buduneli; Eralp Buduneli; Emel Öykü Çetin; Levent Kirilmaz; Necil Kutukculer

Objective: To evaluate the effects of adjunctive meloxicam administration on clinical periodontal measurements and gingival crevicular fluid (GCF) prostaglandin E2 (PGE2) and interleukin-1-beta (IL-1β) levels in chronic periodontitis. Methods: Forty chronic periodontitis patients were randomized to receive either meloxicam 7.5 mg or placebo tablets for 10 days with scaling and root planing (SRP). GCF levels of PGE2 and IL-1β at baseline, day 10 of drug intake and 4 weeks after SRP were determined by enzyme-linked immunosorbent assay. Demographic, clinical periodontal data were analyzed using a repeated measures ANOVA and Bonferroni analysis. GCF PGE2 and IL-1β levels were compared between different evaluation times using the Friedman test. The Mann–Whitney test was used to compare biochemical data between the study groups. Pearson correlation analysis was used to relate clinical and biochemical data. Results: Study groups showed significant reductions in all clinical periodontal measurements and GCF volume (p < 0.05). In both groups, IL-1β was reduced significantly on day 10 and at week 4 compared with baseline (p < 0.01) without significant changes in PGE2 levels (p > 0.05). No significant differences were found between study groups in GCF IL-1β or PGE2 levels (p > 0.05). Conclusion: Adjunctive meloxicam does not seem to provide additional improvement in clinical parameters or GCF PGE2 and IL-1β levels. Larger-scale studies may better clarify potential usage of anti-inflammatory agents in periodontal therapy.


Archives of Oral Biology | 2013

Gingival crevicular fluid and serum levels of APRIL, BAFF and TNF-alpha in rheumatoid arthritis and osteoporosis patients with periodontal disease

Pınar Gümüş; Eralp Buduneli; Başak Bıyıkoğlu; Kenan Aksu; Fulden Sarac; Nurcan Buduneli; David F. Lappin

BACKGROUND This study was performed to evaluate gingival crevicular fluid (GCF) and serum levels of a proliferation inducing ligand (APRIL) and B cell activating factor (BAFF) and compare this to differences between TNF-alpha levels in rheumatoid arthritis (RA), osteoporosis (OPR) and systemically healthy women with periodontal disease (SH). DESIGN Gingival crevicular fluid (GCF) and serum samples were obtained before any periodontal intervention from 17 RA, 19 OPR patients and 13 SH women with periodontitis. Full-mouth clinical periodontal measurements were recorded. APRIL, BAFF and TNF-α levels were determined by ELISA. Statistical analysis was performed using multivariate analysis, ANOVA and Spearman correlation. RESULTS Pocket depths differed in site-specific comparisons, but otherwise clinical measurements were similar in the three study groups. Multivariate least squares regression ANOVA adjusted for age and for plaque index indicated that total amounts of TNF-α and concentrations of TNF-α, BAFF and APRIL were significantly greater in the RA patients than in the SH group (p<0.05), and GCF concentrations of BAFF were greater in OPR patients than in SH. Serum TNF-α and BAFF were significantly higher in the RA group compared to SH (p<0.05) and serum TNF-α was greater in RA than in OPR (p<0.05). APRIL and BAFF correlated with RANKL levels in GCF and serum (p<0.05). CONCLUSION Despite long-term usage of anti-inflammatory drugs in the RA and OPR patients, increased TNF-family cytokines, might suggest that these patients have a propensity to overproduce these inflammatory mediators but whether this results from greater disease activity or contribute to greater disease activity remains moot.


Journal of Periodontal Research | 2012

Acute myocardial infarction elevates serine protease activity in saliva of patients with periodontitis

Päivi Mäntylä; Eralp Buduneli; Gülnur Emingil; Taina Tervahartiala; Pirkko J. Pussinen; Nezihi Baris; Azem Akilli; Gül Atilla; Timo Sorsa

BACKGROUND AND OBJECTIVE There are indications that acute myocardial infarction (AMI) may have an effect on the oral environment, which is reflected in the expression of salivary and gingival proteinases. According to our knowledge, no studies have been carried out to investigate the effect of AMI on the activities of two major tissue-destructive serine protease and microbial effectors, elastase and cathepsin G, produced by oral fluid polymorphonuclear granulocytes (PMN). Therefore, we compared the activities of elastase and cathepsin G in saliva from patients with AMI and from systemically healthy subjects (non-AMI) with similar periodontal conditions. MATERIAL AND METHODS A total of 92 patients (47 AMI and 28 non-AMI patients with gingivitis or periodontitis, and 17 systemically and periodontally healthy subjects as a control group) were recruited. Clinical periodontal measurements were recorded, and stimulated whole-saliva samples were collected. The patients with AMI were clinically examined within 3-4 d after admission to the coronary care unit. The activities of saliva neutrophil elastase and cathepsin G were measured after collection, at specific time-points during incubation (from baseline to 23 h) by specific synthetic peptide substrate assays. RESULTS The saliva of patients with AMI and periodontitis had a significant trend for the highest elastase activities among the study groups. Elastase and cathepsin G activities correlated significantly with each other in the AMI periodontitis group (r = 0.8, p < 0.01). In a logistic regression analysis, the level of salivary elastase activity associated significantly with periodontitis. CONCLUSION AMI may be reflected in PMN serine protease elastase activity in saliva, despite its strong association with periodontitis.


Journal of Periodontology | 2006

Effects of Selective Cyclooxygenase-2 Inhibitor and Omega-3 Fatty Acid on Serum Interleukin-1β, Osteocalcin, and C-Reactive Protein Levels in Rats

Saynur Vardar-Sengul; Nurcan Buduneli; Eralp Buduneli; Haluk Baylas; Gül Atilla; David F. Lappin; Denis F. Kinane

BACKGROUND The aim of this study was to evaluate the effects of selective cyclooxygenase-2 inhibitor, celecoxib, and omega-3 fatty acid on serum levels of interleukin 1-beta (IL-1β), osteocalcin (OC), and C-reactive protein (CRP) in experimental periodontitis. METHODS Experimental periodontitis in rats was induced by repeated injection of purified lipopolysaccharide (LPS) derived from Escherichia coli endotoxin. Forty-seven adult male Sprague-Dawley rats were divided into five study groups as follows: saline control, LPS, LPS + celecoxib, LPS + omega-3 fatty acid, and LPS + celecoxib + omega-3 fatty acid. Celecoxib and omega-3 fatty acid were given alone or in combination during 14 days of the experimental study period. At the end of the 2-week protocol, serum samples were obtained, and the rats were sacrificed. Serum samples were analyzed for IL-1β, OC, and CRP concentrations by enzyme-linked immunosorbent assay. Defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by non-parametric tests. RESULTS According to the morphometric measurements, the LPS and drug treatment groups showed significantly higher bone loss than the saline control group (P <0.05). Omega-3 fatty acid, both alone and in combination with celecoxib, revealed significantly higher IL-1β levels than LPS and celecoxib groups (P <0.05). Individual and combined administration of celecoxib and omega-3 fatty acid significantly increased OC levels compared to the LPS group (P <0.05). There were no significant differences in serum CRP levels. CONCLUSIONS Celecoxib and/or omega-3 fatty acid administration does not significantly influence circulating levels of CRP. The significantly increased serum OC level observed after individual and combination administration suggests that celecoxib and omega-3 fatty acid may influence bone remodeling and thereby inhibit the progression of alveolar bone resorption. However, the failure to observe any significant inhibition of bone loss in celecoxib- and/or omega-3 fatty acid-treated rats compared to the LPS group suggests that their therapeutic effect may be reduced by other factors, such as increases in serum IL-1β promoting osteoclast activity.

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Denis F. Kinane

University of Pennsylvania

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Timo Sorsa

University of Helsinki

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