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Öğe The actin-bundling protein L-plastin: a novel local inflammatory marker associated with periodontitis(Wiley, 2015) Ozturk, V. O.; Emingil, G.; Osterwalder, V.; Bostanci, N.Background and ObjectiveL-plastin, an actin-bundling protein, is exclusively expressed in leukocytes and plays a crucial role in immune-mediated events. Periodontitis is a common infectious inflammatory disease that destroys the tooth-supporting tissues. Recent findings using proteomic technologies have demonstrated that L-plastin is one of the few molecules consistently present in the inflammatory exudate of the gingiva in periodontal disease, but not in health. Therefore, this study aimed to investigate in detail the local and systemic role of this molecule in different forms of periodontitis. Material and MethodsA total of 61 subjects who met the inclusion/exclusion criteria were recruited, including 21 with chronic periodontitis, 20 generalized aggressive periodontitis and 20 nonperiodontitis control subjects. Gingival tissue biopsies, gingival crevicular fluid, as well as serum and saliva, were obtained. Immunohistochemistry and quantitative real-time PCR were employed to evaluate the localization and mRNA expression, respectively, of L-plastin. L-plastin levels in gingival crevicular fluid, saliva and serum were measured using ELISA. Statistical analysis was performed using nonparametric methods. ResultsSubjects with chronic periodontitis and generalized aggressive periodontitis exhibited significantly higher tissue L-plastin gene expression and gingival crevicular fluid levels than did subjects in the control group but there was no significant difference between the two forms of periodontitis. Within gingival tissue, L-plastin was confined to the inflammatory infiltrate. There was no statistically significant difference between serum and salivary L-plastin levels among the three study groups. ConclusionThe elevated gingival tissue expression and gingival crevicular fluid levels of L-plastin in both forms of periodontitis may denote the localized involvement of this novel molecule in the pathogenesis of the disease.Öğe The actin-bundling protein L-plastin: a novel local inflammatory marker associated with periodontitis(Wiley, 2015) Ozturk, V. O.; Emingil, G.; Osterwalder, V.; Bostanci, N.Background and ObjectiveL-plastin, an actin-bundling protein, is exclusively expressed in leukocytes and plays a crucial role in immune-mediated events. Periodontitis is a common infectious inflammatory disease that destroys the tooth-supporting tissues. Recent findings using proteomic technologies have demonstrated that L-plastin is one of the few molecules consistently present in the inflammatory exudate of the gingiva in periodontal disease, but not in health. Therefore, this study aimed to investigate in detail the local and systemic role of this molecule in different forms of periodontitis. Material and MethodsA total of 61 subjects who met the inclusion/exclusion criteria were recruited, including 21 with chronic periodontitis, 20 generalized aggressive periodontitis and 20 nonperiodontitis control subjects. Gingival tissue biopsies, gingival crevicular fluid, as well as serum and saliva, were obtained. Immunohistochemistry and quantitative real-time PCR were employed to evaluate the localization and mRNA expression, respectively, of L-plastin. L-plastin levels in gingival crevicular fluid, saliva and serum were measured using ELISA. Statistical analysis was performed using nonparametric methods. ResultsSubjects with chronic periodontitis and generalized aggressive periodontitis exhibited significantly higher tissue L-plastin gene expression and gingival crevicular fluid levels than did subjects in the control group but there was no significant difference between the two forms of periodontitis. Within gingival tissue, L-plastin was confined to the inflammatory infiltrate. There was no statistically significant difference between serum and salivary L-plastin levels among the three study groups. ConclusionThe elevated gingival tissue expression and gingival crevicular fluid levels of L-plastin in both forms of periodontitis may denote the localized involvement of this novel molecule in the pathogenesis of the disease.Öğe The actin-bundling protein L-plastin: a novel local inflammatory marker associated with periodontitis(Wiley, 2015) Ozturk, V. O.; Emingil, G.; Osterwalder, V.; Bostanci, N.Background and ObjectiveL-plastin, an actin-bundling protein, is exclusively expressed in leukocytes and plays a crucial role in immune-mediated events. Periodontitis is a common infectious inflammatory disease that destroys the tooth-supporting tissues. Recent findings using proteomic technologies have demonstrated that L-plastin is one of the few molecules consistently present in the inflammatory exudate of the gingiva in periodontal disease, but not in health. Therefore, this study aimed to investigate in detail the local and systemic role of this molecule in different forms of periodontitis. Material and MethodsA total of 61 subjects who met the inclusion/exclusion criteria were recruited, including 21 with chronic periodontitis, 20 generalized aggressive periodontitis and 20 nonperiodontitis control subjects. Gingival tissue biopsies, gingival crevicular fluid, as well as serum and saliva, were obtained. Immunohistochemistry and quantitative real-time PCR were employed to evaluate the localization and mRNA expression, respectively, of L-plastin. L-plastin levels in gingival crevicular fluid, saliva and serum were measured using ELISA. Statistical analysis was performed using nonparametric methods. ResultsSubjects with chronic periodontitis and generalized aggressive periodontitis exhibited significantly higher tissue L-plastin gene expression and gingival crevicular fluid levels than did subjects in the control group but there was no significant difference between the two forms of periodontitis. Within gingival tissue, L-plastin was confined to the inflammatory infiltrate. There was no statistically significant difference between serum and salivary L-plastin levels among the three study groups. ConclusionThe elevated gingival tissue expression and gingival crevicular fluid levels of L-plastin in both forms of periodontitis may denote the localized involvement of this novel molecule in the pathogenesis of the disease.Öğe Clinical, oral immunological and microbiological shifts during and after pregnancy(Springer Science and Business Media Deutschland GmbH, 2024) Meriç, P.; Silbereisen, A.; Emingil, G.; Öztürk, V.-Ö.; Bostanci, N.Objectives: Physiological changes and shifts in the oral microbiota composition during pregnancy may affect the maternal immune system. Uncomplicated pregnancy is associated with a T-helper (Th) 2 predominant cytokine regulation (anti-inflammatory), while oral health deterioration during pregnancy is reflected by severe gingival inflammation, a primarily Th1 cytokine phenotype (pro-inflammatory), and oral microbiome alterations. This prospective observational study aimed to evaluate Th cytokine shifts and changes in the oral microbiota composition in saliva of women before and after birth. Material and methods: Saliva (n = 96) was collected before and 6 months after birth, and medical, oral health, and periodontal status were assessed. In a multiplex immunoassay, 10 cytokines were simultaneously analyzed and cumulative Th1 and Th2 cytokine levels and Th1/Th2 ratio were calculated for all groups. Putative periodontal pathogens (n = 6) were evaluated by quantitative real-time polymerase chain reaction. Results: Th2 cytokine levels were significantly lower (p = 0.014) while pro-inflammatory cytokine levels were significantly higher (p < 0.01) during pregnancy than postpartum. Similar Th1 levels were found between the groups (p = 0.143). Th1 and Th2 cytokines positively correlated with periodontal parameters (p < 0.001) and levels of studied bacteria during pregnancy (p < 0.05). Conclusions: This study identified a significantly increased Th1/Th2 cytokine ratio during pregnancy and a positive association with putative periodontal pathogens. This immunological and microbiological deregulation in the oral milieu during pregnancy is suggestive of a destructive inflammatory periodontal profile. Study registration: Clinical Trials.gov (Record BAP-2015). Clinical relevance: Understanding altered oral immunological and microbiological regulation patterns during pregnancy may help improve the inflammatory periodontal profile in pregnant women. © 2023, The Author(s).Öğe Differential expression of receptor activator of nuclear factor-kappa B ligand and osteoprotegerin mRNA in periodontal diseases(Wiley, 2007) Bostanci, N.; Ilgenli, T.; Emingil, G.; Afacan, B.; Han, B.; Toz, H.; Berdeli, A.; Atilla, G.; McKay, I. J.; Hughes, F. J.; Belibasakis, G. N.Background and Objective: Receptor activator of nuclear factor-kappa B ligand (RANKL) is responsible for the induction of osteoclastogenesis and bone resorption, whereas its decoy receptor, osteoprotegerin, can directly block this action. Because this dyad of cytokines is crucial for regulating the bone remodelling process, imbalances in their expression may cause a switch from the physiological state to enhanced bone resorption or formation. This study investigated the mRNA expression of RANKL and osteoprotegerin, as well as their relative ratio, in the gingival tissues of patients with various forms of periodontal diseases. Material and Methods: Gingival tissue was obtained from nine healthy subjects and 41 patients, who had gingivitis, chronic periodontitis, generalized aggressive periodontitis, and chronic periodontitis and were receiving immunosuppressant therapy. Quantitative real- time polymerase chain reaction was employed to evaluate the mRNA expression of RANKL and osteoprotegerin in these tissues. Results: Compared with healthy individuals, patients in all periodontitis groups, but not those with gingivitis, exhibited stronger RANKL expression and a higher relative RANKL/osteoprotegerin ratio. In addition, osteoprotegerin expression was weaker in patients with chronic periodontitis. When patients with generalized aggressive periodontitis and chronic periodontitis were compared, the former exhibited stronger RANKL expression, whereas the latter exhibited weaker osteoprotegerin expression, and there was no difference in their relative ratio. When chronic periodontitis patients were compared with chronic periodontitis patients receiving immunosuppressant therapy, osteoprotegerin, but not RANKL, expression was stronger in the latter. Conclusion: This study demonstrates that RANKL and osteoprotegerin expression are differentially regulated in various forms of periodontitis, and the relative RANKL/osteoprotegerin ratio appears to be indicative of disease occurrence. This information may confer diagnostic and therapeutic value in periodontitis.Öğe Elevated Oral and Systemic Levels of Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) in Periodontitis(Sage Publications Inc, 2013) Bostanci, N.; Ozturk, V. O.; Emingil, G.; Belibasakis, G. N.The Triggering Receptor Expressed on Myeloid cells 1 (TREM-1) is a cell-surface receptor of the immunoglobulin superfamily, involved in the propagation of the inflammatory response to bacterial challenge. Soluble (s) TREM-1 is released from the cell surface during the course of infection and is a useful inflammatory biomarker in the early diagnosis of systemic sepsis. The hypothesis of this study was that oral and systemic levels of sTREM-1 are elevated in periodontitis. Therefore, the aim was to investigate, by ELISA, the sTREM-1 concentrations in saliva and serum of individuals without periodontitis (control) and persons with chronic or generalized aggressive periodontitis. In saliva, sTREM-1 concentrations were higher in chronic and aggressive periodontitis than in the control group, by 3.3-fold and 5.6-fold, respectively. In serum, these differences were 1.7-fold and 2-fold, respectively. However, there were no significant differences between the two forms of periodontitis, neither in saliva nor in serum. Salivary and serum sTREM-1 levels positively correlated with full-mouth clinical periodontal parameters. In conclusion, the increased oral and systemic levels of sTREM-1 in periodontitis denote a value for this molecule as a biomarker for the disease and may also have implications in the association between periodontal infections and systemic inflammatory response.Öğe Elevated Oral and Systemic Levels of Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) in Periodontitis(Sage Publications Inc, 2013) Bostanci, N.; Ozturk, V. O.; Emingil, G.; Belibasakis, G. N.The Triggering Receptor Expressed on Myeloid cells 1 (TREM-1) is a cell-surface receptor of the immunoglobulin superfamily, involved in the propagation of the inflammatory response to bacterial challenge. Soluble (s) TREM-1 is released from the cell surface during the course of infection and is a useful inflammatory biomarker in the early diagnosis of systemic sepsis. The hypothesis of this study was that oral and systemic levels of sTREM-1 are elevated in periodontitis. Therefore, the aim was to investigate, by ELISA, the sTREM-1 concentrations in saliva and serum of individuals without periodontitis (control) and persons with chronic or generalized aggressive periodontitis. In saliva, sTREM-1 concentrations were higher in chronic and aggressive periodontitis than in the control group, by 3.3-fold and 5.6-fold, respectively. In serum, these differences were 1.7-fold and 2-fold, respectively. However, there were no significant differences between the two forms of periodontitis, neither in saliva nor in serum. Salivary and serum sTREM-1 levels positively correlated with full-mouth clinical periodontal parameters. In conclusion, the increased oral and systemic levels of sTREM-1 in periodontitis denote a value for this molecule as a biomarker for the disease and may also have implications in the association between periodontal infections and systemic inflammatory response.Öğe Expression and regulation of the NALP3 inflammasome complex in periodontal diseases(Wiley, 2009) Bostanci, N.; Emingil, G.; Saygan, B.; Turkoglu, O.; Atilla, G.; Curtis, M. A.; Belibasakis, G. N.Periodontitis is an infectious process characterized by inflammation affecting the supporting structures of the teeth. Porphyromonas gingivalis is a major oral bacterial species implicated in the pathogenesis of periodontitis. Processing of interleukin (IL)-1 family cytokines is regulated by an intracellular innate immune response system, known as the NALP3 [nacht domain-, leucine-rich repeat-, and pyrin domain (PYD)-containing protein 3] inflammasome complex. The aim of the present study was to investigate by quantitative real-time polymerase chain reaction (PCR) the mRNA expression of NALP3, its effector molecule apoptosis associated speck-like protein (ASC), its putative antagonist NLRP2 (NLR family, PYD-containing protein 2), IL-1 beta and IL-18 (i) in gingival tissues from patients with gingivitis (n = 10), chronic periodontitis (n = 18), generalized aggressive periodontitis (n = 20), as well as in healthy subjects (n = 20), (ii) in vitro in a human monocytic cell line (Mono-Mac-6), in response to P. gingivalis challenge for 6 h. The clinical data indicate that NALP3 and NLRP2, but not ASC, are expressed at significantly higher levels in the three forms of inflammatory periodontal disease compared to health. Furthermore, a positive correlation was revealed between NALP3 and IL-1 beta or IL-18 expression levels in these tissues. The in vitro data demonstrate that P. gingivalis deregulates the NALP3 inflammasome complex in Mono-Mac-6 cells by enhancing NALP3 and down-regulating NLRP2 and ASC expression. In conclusion, this study reveals a role for the NALP3 inflammasome complex in inflammatory periodontal disease, and provides a mechanistic insight to the host immune responses involved in the pathogenesis of the disease by demonstrating the modulation of this cytokine-signalling pathway by bacterial challenge.Öğe Expression and regulation of the NALP3 inflammasome complex in periodontal diseases(Wiley, 2009) Bostanci, N.; Emingil, G.; Saygan, B.; Turkoglu, O.; Atilla, G.; Curtis, M. A.; Belibasakis, G. N.Periodontitis is an infectious process characterized by inflammation affecting the supporting structures of the teeth. Porphyromonas gingivalis is a major oral bacterial species implicated in the pathogenesis of periodontitis. Processing of interleukin (IL)-1 family cytokines is regulated by an intracellular innate immune response system, known as the NALP3 [nacht domain-, leucine-rich repeat-, and pyrin domain (PYD)-containing protein 3] inflammasome complex. The aim of the present study was to investigate by quantitative real-time polymerase chain reaction (PCR) the mRNA expression of NALP3, its effector molecule apoptosis associated speck-like protein (ASC), its putative antagonist NLRP2 (NLR family, PYD-containing protein 2), IL-1 beta and IL-18 (i) in gingival tissues from patients with gingivitis (n = 10), chronic periodontitis (n = 18), generalized aggressive periodontitis (n = 20), as well as in healthy subjects (n = 20), (ii) in vitro in a human monocytic cell line (Mono-Mac-6), in response to P. gingivalis challenge for 6 h. The clinical data indicate that NALP3 and NLRP2, but not ASC, are expressed at significantly higher levels in the three forms of inflammatory periodontal disease compared to health. Furthermore, a positive correlation was revealed between NALP3 and IL-1 beta or IL-18 expression levels in these tissues. The in vitro data demonstrate that P. gingivalis deregulates the NALP3 inflammasome complex in Mono-Mac-6 cells by enhancing NALP3 and down-regulating NLRP2 and ASC expression. In conclusion, this study reveals a role for the NALP3 inflammasome complex in inflammatory periodontal disease, and provides a mechanistic insight to the host immune responses involved in the pathogenesis of the disease by demonstrating the modulation of this cytokine-signalling pathway by bacterial challenge.Öğe Host Immune Response to Dental Implants(Springer International Publishing, 2022) Bostanci, N.; Silberiesen, A.; Bao, K.; Gurkan, A.Biocompatibility and biostability are the key properties of dental implants in the “oral environment,” in order to optimize their performance before or after functional loading. Uneventful host defense to dental implant insertion starts with a more favorable immune response that promotes wound healing around the jawbone and soft mucosal tissue. The growth of a biofilm on the surface of an implant is an igniting factor of the inflammatory response of the surrounding peri-implant tissues. At an initial stage, peri-implant mucositis is established, whereas the spread of inflammation towards the supportive bone leads to peri-implantitis. The molecular content of peri-implant crevicular fluid (PICF) offers a medium for “measurable biological indicators” of peri-implant diseases and potentially new targets for the immunomodulatory treatment of peri-implant diseases. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.Öğe Oral health and oral quality of life in inactive patients with familial Mediterranean fever without amyloidosis(Clinical & Exper Rheumatology, 2013) Sogur, E.; Onem, E.; Kalfa, M.; Emmungil, H.; Bostanci, N.; Aksu, K.; Baksi, B. G.; Keser, G.; Direskeneli, H.; Mumcu, G.Objectives. The aim of this study was to investigate oral and general health-related quality of life (QoL) in patients with familial Mediterranean fever (FMF) disease. Methods. In this cross-sectional study, 45 patients with FMF, 50 age- and sex-matched healthy controls (HC), and 50 patients with Behcet's disease (BD) as the disease control group were included. FMF disease activity was evaluated by using the FMF-severity score, as well as with erythrocyte sedimentation rate (ESR), and serum C-reactive protein and fibrinogen levels. Oral health-related QoL and general QoL were evaluated using oral health impact profile-14 (OHIP-14) and Medical Outcomes Short-Form Health Survey Questionnaire 36 (SF-36), respectively. Results. Only the numbers of extracted teeth (4.13 +/- 4.72 vs. 1.55 +/- 3.6) and filled teeth (2.33 +/- 3.19 vs. 0.66 +/- 1.46) were significantly higher in FMF group compared to HC group (p=0.005 and p=0.013, respectively). OHIP-14 score was significantly higher in FMF and BD groups compared to HC group. In FMF patients, OHIP-14 score was positively correlated with the number of extracted teeth (r=0.38, p=0.010), while the number of carious teeth was positively correlated with ESR (r=0.43, p=0.003). When FMF patients were sub-classified according to disease severity, no significant difference was observed with respect to oral health status. Conclusion. In patients with FMF, some of the parameters of oral health status were found to be worse compared to HC group. Tooth loss appears to be to be a critical factor contributing to impaired oral QoL. In general, oral health status in FMF patients is better than in BD patients.Öğe Salivary inflammatory burden in pre- and postmenopausal women: Associations with body mass index, patient-reported health, serum cytokines, and periodontal parameters(John Wiley and Sons Inc, 2023) Yakar, N.; Bostanci, N.; Özdemir, G.; Atmaca, H.; Türedi, A.; Şahin, Ç.; Köse, T.Background: The decline of estrogen levels during menopause impacts weight, mood, and overall health, both orally and systemically. This study assessed salivary levels of tumor necrosis factor alpha (TNF-?), interleukin-6 (IL-6), IL-10, and IL-7 in postmenopausal (PMW) and regularly menstruating premenopausal (RMPW) women, while considering serum cytokine levels, body mass index (BMI), periodontal health, and self-reported physical and emotional well-being. Methods: In this study, 75 PMW and 71 RMPW were included. Clinical and periodontal parameters were evaluated, and perceived health was assessed with the Women's Health Questionnaire (WHQ). Cytokine levels in both saliva and serum were quantified by enzyme-linked immunosorbent assay (ELISA). Covariate evaluations of salivary cytokines were conducted using hierarchical linear regression modeling. Results: Cytokines were detectable in saliva from 71 PMW and 67 RMPW. In the initial unadjusted model, IL-7, IL-10, and TNF-? exibited significant differences between RMPW and PMW. However, these differences became non-significant (p > 0.05) in the final model after adjusting for age, which implies a negligible effect of the investigated covariates on salivary cytokine levels when age was considered. Lower levels of IL-6 in PMW, which initially showed no significant difference, became borderline (p = 0.054) in the final model after adjusting for age. Conclusions: After adjusting for multiple factors, no significant difference was found in the salivary levels of the investigated cytokines between RMPW and PMW. Factors such as BMI, perceived health, serum cytokine levels, and periodontal parameters seem to minimally influence these levels in PMW. However, age may be a stronger confounding factor. © 2023 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.Öğe Synergistetes cluster A in saliva is associated with periodontitis(Wiley-Blackwell, 2013) Belibasakis, G. N.; Oztuerk, V. -O.; Emingil, G.; Bostanci, N.Background and ObjectivesSynergistetes is a novel bacterial phylum consisting of gram-negative anaerobes. Increasing lines of evidence demonstrate that this phylum is associated with periodontal diseases. This study aimed to compare the presence and levels of Synergistetes clusters A and B, in saliva of patients with chronic periodontitis (CP), generalized aggressive periodontitis (G-AgP) and non-periodontitis subjects, and investigate their correlation with clinical parameters. Material and MethodsSaliva was collected from patients with CP (n=20), G-AgP (n=21) and non-periodontitis subjects (n=18). Full mouth clinical periodontal measurements were recorded. The numbers of Synergistetes cluster A and cluster B or the associated species Jonquetella anthropi were quantified by fluorescent in situ hybridization and microscopy. ResultsSynergistetes cluster A bacteria were detected more frequently, and at higher numbers and proportions in the two periodontitis groups, than the non-periodontitis control group. The prevalence was 27.7% in the control group, 85% in CP and 86% in G-AgP. Compared to the control group, the numbers were significantly higher by 12.5-fold in CP and 26.5-fold in G-AgP, whereas the difference between the two forms of periodontitis was not statistically significant. Within the total bacterial population, the proportion of this cluster was increased in CP and G-AgP compared to the control group, with the difference between the two forms of periodontitis being also significant. There was a positive correlation between the levels of Synergistetes cluster A in saliva and all full mouth clinical periodontal parameters. Nevertheless, Synergistetes cluster B bacteria and J.anthropi species were detected infrequently and at low levels in all the three subject groups. ConclusionSynergistetes cluster A, but not cluster B, bacteria are found at higher prevalence, numbers and proportions in saliva from patients with periodontitis, than non-periodontitis subjects. These findings support the association of this cluster with periodontitis.Öğe Tumor necrosis factor-alpha-converting enzyme (TACE) levels in periodontal diseases(Int Amer Assoc Dental Researchi A D R/A A D R, 2008) Bostanci, N.; Emingil, G.; Afacan, B.; Han, B.; Ilgenli, T.; Atilla, G.; Hughes, F. J.; Belibasakis, G. N.Tumor necrosis factor-alpha- converting enzyme ( TACE) is a metalloprotease which can shed several cytokines from the cell membrane, including receptor activator of NF-kappa B ligand ( RANKL). This study aimed to investigate the hypothesis that TACE would be elevated in the gingival crevicular fluid ( GCF) of persons with periodontitis. Total TACE amounts in GCF were higher in persons with chronic and aggressive periodontitis than in those with gingivitis or in healthy persons. TACE concentrations in GCF were higher in persons with chronic and aggressive periodontitis than in those with gingivitis, although not significantly higher than in healthy persons. Persons with chronic periodontitis receiving immunosuppressive treatment exhibited over 10-fold lower TACE levels than the other periodontitis groups. TACE was positively correlated with probing pocket depth, clinical attachment levels, and RANKL concentrations in GCF. In conclusion, the increased GCF TACE levels in persons with periodontitis and their positive correlation with RANKL may indicate an association of this enzyme with alveolar bone loss, and may warrant special attention in future therapeutic approaches.
