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ABSTRACT: Objective: Molecular biomarkers are searched for diagnostic use in periodontal diseases. The aim of our study was to explore different gingival crevicular fluid (GCF) matrix metalloproteinase (MMP) -8 patterns in smoking and non-smoking chronic periodontitis (CP) patients and to test the utility of baseline GCF MMP-8 levels in predicting categorically assessed treatment outcomes. Materials and Methods: Study population comprised of 15 CP patients (5 non-smokers and 10 smokers). GCF sampling from 5 to 7 selected periodontal sites per patient was done at baseline, post treatment control and bimonthly during the maintenance period visits ad 8-12 months. GCF MMP-8 levels were measured with an immunofluorometric assay (IFMA). Different MMP-8 response patterns were explored by cluster analysis. The ability of baseline MMP-8 levels to predict the categorical treatment outcomes were analysed with receiver operating characteristic (ROC) analysis Results: GCF MMP-8 response patterns could be clustered into two different site profiles among both smokers and non-smokers. Smokers´ site profiles -1 and -2 had significantly different clinical attachment level and gingival recession changes by the end of the maintenance period. In smokers´ sites baseline MMP-8 levels predicted significantly the categorical treatment outcome. Conclusion: Baseline GCF MMP-8 level predicts strongly how MMP-8 level behaves during the maintenance period. In smokers' sites high baseline MMP-8 levels indicate weak treatment response.
Journal of Periodontology 05/2013; · 2.60 Impact Factor
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ABSTRACT: Background: In this cross-sectional study we characterized the association between subgingival bacterial profile and periodontal parameters in patients assigned to coronary angiography due to cardiologic problems, which may affect the oral microbiota. Methods: Pooled subgingival bacterial samples were collected from 477 dentate subjects during the oral examinations with periodontal probing depths (PD), bleeding on probing (BOP), and assessments of radiographic alveolar bone loss (ABL). The checkerboard DNA-DNA hybridization assay was used to determine the levels of 29 oral bacteria, which were divided into three bacterial complexes. Results: All bacterial combinations from the etiological bacterial group and each species from the red complex associated significantly (p < 0.001) with the grades of ABL. The prevalence of etiological bacterial group and the level of each species associated also strongly with the proportion of sites with PD 4-5 mm and ≥ 6 mm, BOP, and ABL except, A. actinomycetemcomitans. The level of gram-negative oral bacteria correlated significantly with that of gram-positive (r = 0.840, p < 0.001). In the multiple logistic regression analysis, the prevalence of the etiological bacterial group, the levels of gram-negative bacteria and Treponema denticola, and the prevalence of Porphyromonas gingivalis and T. denticola associated significantly with ABL, while other bacterial complexes or the level of gram-positive species did not. Conclusions: Although the levels of gram-negative and gram-positive species paralleled with periodontal parameters, only the species considered etiological were associated with the ABL.
Journal of Periodontology 03/2013; · 2.60 Impact Factor
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ABSTRACT: AIM: We investigated the association between angiographically verified coronary artery disease (CAD) and subgingival Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola. MATERIALS AND METHODS: The cross-sectional study population (n = 445) comprised 171 (38.4%) patients with Stable CAD, 158 (35.5%) with acute coronary syndrome (ACS) and 116 (26.1%) with no significant CAD (No CAD). All patients participated in clinical and radiological oral health examinations. Pooled subgingival bacterial samples were analysed by checkerboard DNA-DNA hybridization assays. RESULTS: In all study groups, the presence of P. gingivalis, T. forsythia and T. denticola indicated a significant (p ≤ 0.001) linear association with the extent of alveolar bone loss (ABL), but A. actinomycetemcomitans did not (p = 0.074). With a threshold level of bacterial cells 1 × 10(5) A. actinomycetemcomitans was significantly more prevalent in the Stable CAD group (42.1%) compared to the No CAD group (30.2%) (p = 0.040). In a multi-adjusted logistic regression analysis using this threshold, A. actinomycetemcomitans positivity associated with Stable CAD (OR 1.83, 95% CI 1.00-3.35, p = 0.049), but its level or levels of other bacteria did not. CONCLUSIONS: The presence of subgingival A. actinomycetemcomitans associates with an almost twofold risk of Stable CAD independently of alveolar bone loss.
Journal Of Clinical Periodontology 02/2013; · 3.00 Impact Factor
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ABSTRACT: The aim of this study was to investigate the association between angiographically verified coronary artery disease (CAD) and salivary levels of four major periodontal pathogens.
The study population (n = 492) was composed of 179 (36.4%) patients with stable CAD, 166 (33.7%) with acute coronary syndrome (ACS), and 119 (24.2%) showing no pathological findings by coronary angiography. All patients were subjected to a detailed oral health examination. The saliva samples were analyzed for lipopolysaccharide activity as well as for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, and Tannerella forsythia by quantitative PCR. Serum antibodies levels against A. actinomycetemcomitans were analyzed.
The level of bacterial burden was linearly associated with alveolar bone loss (p < 0.001) and bleeding on probing (p = 0.015). The median salivary levels of A. actinomycetemcomitans in pathogen-positive patients were significantly higher in the "Stable CAD" (p = 0.014) and the "ACS" (p = 0.044) groups when compared to "No significant CAD" patients. In logistic regression models, a 10-fold increase in the salivary A. actinomycetemcomitans levels was associated with a risk for stable CAD and ACS with odds ratios (ORs) of 7.47 (95% confidence interval [CI]: 1.57-35.5, p = 0.012) and 4.31 (95% CI: 1.06-17.5, p = 0.041), respectively. The OR for the association of IgA-class antibody levels against A. actinomycetemcomitans with ACS risk was 3.13 (95% CI: 1.38-7.12, p = 0.006)/log(10) unit increase.
High salivary levels of A. actinomycetemcomitans and systemic exposure to the bacterium were associated with increased risk for CAD. These findings emphasize the importance of oral microbiota in cardiovascular risk assessment and therapeutics.
Atherosclerosis 05/2012; 223(2):478-84. · 3.79 Impact Factor
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ABSTRACT: We investigated the association of periodontitis and severity of coronary artery disease (CAD) as verified using coronary angiography.
Participants were recruited among those attending coronary angiography at Helsinki University Central Hospital, Finland, in 2007 and 2008. Detailed clinical periodontal examination [number of teeth, bleeding on probing, periodontal probing depth (PPD)] and oral panoramic radiographs [alveolar bone loss (ABL), angular bone defects] were performed.
Of 506 patients, 123 (24.3%) had no significant CAD, whereas 184 (36.4%) had stable CAD and 169 (33.4%) acute coronary syndrome (ACS). Both stable CAD and ACS were associated with 8-17 missing teeth with ORs 4.33 (1.61-11.7, p = 0.020) and 5.24 (1.90-14.5, p = 0.014), and more than seven teeth with PPD ≥6 mm with ORs 2.44 (1.01-6.07, p = 0.049) and 2.75 (1.16-6.53, p = 0.022) respectively. Severe ABL was associated with ACS with an OR 5.39 (1.23-23.6, p = 0.025). Number of stenosed arteries was linearly associated with ABL (p for trend <0.001), number of missing teeth (p < 0.001), and pockets with probing depth ≥6 mm (p = 0.033).
Compared with patients with no significant stenosis, poor periodontal health including missing teeth, periodontal inflammation, and bone loss is associated with angiographically verified coronary artery narrowing in patients with stable CAD or ACS.
Journal Of Clinical Periodontology 11/2011; 38(11):1007-14. · 3.00 Impact Factor
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ABSTRACT: Sorsa T, Mäntylä P, Tervahartiala T, Pussinen PJ, Gamonal J, Hernandez M. MMP activation in diagnostics of periodontitis and systemic inflammation. J Clin Peridontol 2011; doi: 10.1111/j.1600-051X.2011.01753.x.
Journal Of Clinical Periodontology 06/2011; 38(9):817-9. · 3.00 Impact Factor
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Journal of Periodontology 01/2011; · 2.60 Impact Factor
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ABSTRACT: The aim of this study is to compare salivary and serum biomarker levels and degrees of matrix metalloproteinase (MMP) activation between patients with acute myocardial infarction (AMI) and systemically healthy patients (non-AMI) with similar periodontal conditions.
A total of 92 patients (47 AMI and 28 non-AMI patients with gingivitis or periodontitis; and 17 systemically and periodontally healthy patients as a control group) were recruited. Clinical periodontal measurements were recorded; stimulated whole saliva and serum samples were collected. AMI patients were clinically examined within 3 to 4 days after admission to the coronary care unit. Saliva samples were analyzed for levels of MMP-8, MMP-7, and tissue inhibitor of matrix metalloproteinase (TIMP)-1. Serums were tested for MMP-8, MMP-9, TIMP-1, and TIMP-2 levels by immunofluorometric assay and enzyme-linked immunosorbent assay. Molecular forms and degree of activation of salivary MMP-8, MMP-9, and MMP-13 were analyzed by computer-scanned immunoblots.
Total salivary MMP-8 assessed by immunofluorometric assay method and immunoblot densitometric units was higher in non-AMI than in AMI patients' saliva, but a significantly higher percentage of AMI patients' MMP-8 was activated polymorphonuclear leukocyte (PMN) type (P <0.001) regardless of periodontal diagnosis.Serum MMP-8, MMP-9, and TIMP-1 levels were significantly higher in AMI (for all markers and all comparisons,P <0.05). Characteristic for AMI was dominance of active PMN MMP-8 in saliva [corrected].
Journal of Periodontology 11/2010; 82(5):716-25. · 2.60 Impact Factor
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ABSTRACT: Neutrophil collagenase or collagenase-2 (matrix metalloproteinase [MMP]-8) belongs to the collagenase subgroup of the MMP superfamily of calcium- and zinc-dependent neutral proteinases. MMP-8 is catalytically the most competent proteinase to initiate type I collagen and extracellular matrix degradation associated with periodontal and peri-implant tissue destruction leading to tooth and dental implant loss. Regarding cardiovascular diseases, pathologically excessive MMP-8 has been implicated in atherosclerotic plaque destabilization and rupture probably through its proteolytic ability to thin the protecting collagenous fibrous cap lining coronary and other arteries. During the initiation and course of inflammatory responses in periodontitis, peri-implantitis and cardiovascular diseases, proinflammatory mediators including especially MMP-8 are up-regulated not only in affected tissues but also in the secreted, disease-affected, oral fluids (gingival crevicular fluid [GCF], peri-implant sulcular fluid [PISF], mouthrinse and saliva) as well as in serum and plasma. Regarding periodontitis, peri-implantitis and cardiovascular diseases, the oral fluid and serum MMP-8 analysis has proven to be a sensitive and an objective biomarker as an indicator of health, pathologic processes and pharmacologic response to therapeutic intervention including doxycycline medication as an MMP inhibitor. Oral fluids, i.e., GCF, PISF, mouthrinse and saliva are easily and non-invasively collected for the site- and patient-specific diagnostic analysis in periodontitis and peri-implantitis, whereas serum and/or plasma sample collection is required for diagnosis and monitoring of cardiovascular diseases. Research in periodontology and cardiology has identified a need for the development of innovative point-of-care diagnostic tests for MMP-8. We summarize and review the recent studies on these topics.
Pharmacological Research 10/2010; 63(2):108-13. · 4.44 Impact Factor
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ABSTRACT: Periodontitis is bacterial infection of tooth-supporting tissues leading to inflammation and, subsequently, to loss of teeth. It is one of the most common infections worldwide. Recent studies have shown that periodontal infection may pose a threat to general health by increasing the risk of cardiovascular and lung diseases, and preterm labour. Thus, useful markers of systemic exposure to periodontitis are needed. Markers of periodontitis in serum include those derived directly from periodontopathic pathogens and those originating from the host defence and immune mechanisms. Periodontitis is associated with endotoxemia, which can be directly measured as elevated concentrations of lipopolysaccharide (LPS) in periodontitis patients compared with healthy subjects. Also indirect methods determining endotoxemia, such as elevated concentrations of serum LPS binding protein, soluble CD14, and antibodies to LPS of periodontal pathogens have been reported. Surrogate measures of the host response against periodontal infection, such as matrix metalloproteinases, cytokines, chemokines, inflammation markers, antiphospholipid antibodies, and antibodies to periodontal pathogens, have been used. Of these, however, only antibodies to periodontal pathogens may be seen as specific markers of systemic exposure to periodontopathic pathogens. In this paper we describe and discuss serum markers of periodontitis that have been used for research purposes and/or to support diagnostics. Based on literature review, we encourage research and development of serum screening methods for periodontitis that could be used by general physicians.
Current Medicinal Chemistry 02/2007; 14(22):2402-12. · 4.86 Impact Factor
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TIMO SORSA, PÄIVI MÄNTYLÄ,
HANNE RÖNKÄ,
PEKKA KALLIO,
GUN-BRITT KALLIS,
CHRISTINA LUNDQVIST,
DENIS F. KINANE,
TUULA SALO,
LORNE M. GOLUB,
OLLI TERONEN,
SARI TIKANOJA
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ABSTRACT: Matrix metalloproteinases (MMPs), especially collagenase-2 (MMP-8), are key mediators of irreversible tissue destruction associated with periodontitis and peri-implantitis. MMP-8 is known to exist in elevated amounts and in active form in the gingival crevicular fluid (GCF) and peri-im-plant sulcular fluid (PISF) from progressing periodontitis and peri-implantitis lesions and sites, respectively. (Sorsa et al. Ann. N.Y. Acad. Sci. 737: 112-131 [1994]; Teronen et al. J. Dent. Res. 76: 1529-1537 [1997]). We have developed monoclonal antibodies to MMP-8 (Hanemaaijer et al. J. Biol. Chem. 272: 31504-31509 [1997]) that can be used in a chair-side dipstick test to monitor the course and treatment of periodontitis and peri-implantitis. Monoclonal and polyclonal antibody tests for MMP-8 coincided with the classical functional collagenase activity test from GCF and PISF (Sorsa et al. J. Periodont.Res. 22: 386-393 [1988]) in periodontal and peri-implant health and disease. In future a chair-side functional and/or immunological MMP-test can be useful to diagnose and monitor periodontal and peri-implant disease and health.
Annals of the New York Academy of Sciences 02/2006; 878(1):130 - 140. · 3.15 Impact Factor
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ABSTRACT: Matrix metalloproteinases (MMPs) form a family of enzymes that mediate multiple functions both in the tissue destruction and immune responses related to periodontal inflammation. The expression and activity of MMPs in non-inflamed periodontium is low but is drastically enhanced to pathologically elevated levels due to the dental plaque and infection-induced periodontal inflammation. Soft and hard tissue destruction during periodontitis and peri-implantitis are thought to reflect a cascade of events involving bacterial virulence factors/enzymes, pro-inflammatory cytokines, reactive oxygen species and MMPs. However, recent studies suggest that MMPs can also exert anti-inflammatory effects in defence of the host by processing anti-inflammatory cytokines and chemokines, as well as by regulating apoptotic and immune responses. MMP-inhibitor (MMPI)-drugs, such as doxycycline, can be used as adjunctive medication to augment both the scaling and root planing-treatment of periodontitis locally and to reduce inflammation systematically. Furthermore, MMPs present in oral fluids (gingival crevicular fluid (GCF), peri-implant sulcular fluid (PISF), mouth-rinses and saliva) can be utilized to develop new non-invasive, chair/bed-side, point-of-care diagnostics for periodontitis and dental peri-implantitis.
Annals of Medicine 02/2006; 38(5):306-21. · 3.52 Impact Factor
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ABSTRACT: The role of matrix metalloproteinases (MMPs) in response to mechanical forces in orthodontic tooth movement has only been partially clarified. In the present in vivo pilot study, the presence, levels, and degree of activation of MMP-1 and -8 were measured daily for 1 month in gingival crevicular fluid (GCF) of patients treated with orthodontic fixed appliances. GCF samples were collected from five orthodontic patients and three controls from one upper or lower central incisor or from one upper canine before fixed appliance activation and every 24 hours for 1 month thereafter. The molecular forms and activation degrees of MMP-1 and -8 in GCF were analysed by Western blotting, and MMP-8 levels determined by immunofluorometric assay (IFMA).IFMA revealed, during the study period, on average 12-fold higher levels (56 +/- 50 versus 4.6 +/- 4 microg/l) of MMP-8 in orthodontic GCF than in control GCF. The MMP-8 levels in orthodontic GCF were lower than those detected in gingivitis and periodontitis GCF, but significantly higher than in control GCF. IFMA analysis was confirmed by Western blot analysis showing elevated MMP-8 levels from orthodontic GCF relative to control GCF. Forty-one per cent of total MMP-8 immunoreactivities were high-molecular weight complexes (>100 kDa), 32 per cent in the 75 kDa pro-polymorphonuclear (PMN)-MMP-8 form, 14 per cent in the 60 kDa active-PMN-MMP-8 form, and 13 per cent in the 55 kDa fibroblast-type pro-MMP-8 form. In the GCF of orthodontic patients no MMP-1 immunoreactivities were detected. MMP-8 and -1 levels in the control GCF were low and not detectable. These results demonstrate that in vivo in human GCF, elevation and partial activation of multiple species of PMN- and fibroblast-type MMP-8 reflect periodontal remodelling during orthodontic tooth movement.
The European Journal of Orthodontics 04/2005; 27(2):202-7. · 0.89 Impact Factor
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ABSTRACT: A rapid chair-side test based on the immunological detection of elevated levels of collagenase-2 (matrix metalloproteinase-8, MMP-8) in gingival crevicular fluid (GCF) was developed to identify and monitor the course and treatment of adult periodontitis.
MMP-8 was determined in GCF from periodontitis (11 patients, 90 sites), gingivitis (10 patients, 58 sites) and healthy control (8 patients, 59 sites) sites (i) by a test stick incorporating monoclonal antibodies to two epitopes on MMP-8 and (ii) by measuring MMP-8 concentration by a quantitative immunofluorometric assay. Patients with adult periodontitis were treated by scaling and root planing (SRP) and received oral hygiene instructions. GCF MMP-8 testing and clinical measurements were done before and after SRP.
MMP-8 GCF levels and chair-side test differentiated periodontitis from gingivitis and healthy control sites. MMP-8 GCF levels > 1 mg/l and positive chair-side test identified especially severe periodontitis sites. A positive and negative test stick result, the outcome of which was rapidly detectable in 5 mins, in GCF correlated well with MMP-8 immunofluorometric assay analysis from the collected GCF samples and the severity of periodontitis. Scaling and root planing reduced the MMP-8 levels in severe periodontitis sites with positive MMP-8 test and gingival probing pocket depth (PD) > 5 mm before treatment. The test stick result and the quantitative assay were discrepant in only 18 of the 207 sites tested, thus agreement was very good (kappa = 0.81). With a threshold of 1 mg/l MMP-8 activity the chair-side test provided a sensitivity of 0.83 and specificity of 0.96 (n = 207).
The MMP-8 test can be used to differentiate periodontitis from gingivitis and healthy sites as well as to monitor treatment of periodontitis. A reduction in GCF MMP-8 levels and a change in test stick result provide a means to optimize patient control during maintenance of periodontal treatment.
Journal of Periodontal Research 09/2003; 38(4):436-9. · 1.69 Impact Factor
