Saliva/pathogen biomarker signatures and periodontal disease progression

Department of Periodontics and Oral Medicine, Michigan Center for Oral Health Research, University of Michigan School of Dentistry, 24 Frank Lloyd Wright Dr., Lobby M, Box 422, Ann Arbor, MI 48106 USA.
Journal of dental research (Impact Factor: 4.14). 03/2011; 90(6):752-8. DOI: 10.1177/0022034511399908
Source: PubMed

ABSTRACT The purpose of this study was to determine the role of saliva-derived biomarkers and periodontal pathogens during periodontal disease progression (PDP). One hundred human participants were recruited into a 12-month investigation. They were seen bi-monthly for saliva and clinical measures and bi-annually for subtraction radiography, serum and plaque biofilm assessments. Saliva and serum were analyzed with protein arrays for 14 pro-inflammatory and bone turnover markers, while qPCR was used for detection of biofilm. A hierarchical clustering algorithm was used to group study participants based on clinical, microbiological, salivary/serum biomarkers, and PDP. Eighty-three individuals completed the six-month monitoring phase, with 39 [corrected] exhibiting PDP, while 44 [corrected] demonstrated stability. Participants assembled into three clusters based on periodontal pathogens, serum and salivary biomarkers. Cluster 1 members displayed high salivary biomarkers and biofilm; 71% [corrected] of these individuals were undergoing PDP. Cluster 2 members displayed low biofilm and biomarker levels; 76% [corrected] of these individuals were stable. Cluster 3 members were not discriminated by PDP status; however, cluster stratification followed groups 1 and 2 based on thresholds of salivary biomarkers and biofilm pathogens. The association of cluster membership to PDP was highly significant (p < 0.0007). [corrected] The use of salivary and biofilm biomarkers offers potential for the identification of PDP or stability ( number, CT00277745).

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Available from: Christoph Andreas Ramseier, Jul 30, 2014
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    • "While some authors have not detected any decrease in MMP-9 after non-surgical treatment [8] [41], more recent studies have observed an elevation in MMP-9 and TIMP-1 levels after measuring these markers by ELISA in PD patients [42]. Nevertheless, other articles have verified a drop in MMP-9 levels only 12 months after treatment of moderate periodontitis [43]. Our results evidence that MMP-9 levels are increased in the saliva of PD patients but this is attenuated after periodontal therapy. "
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    ABSTRACT: BACKGROUND: Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases with an important role in physiological and pathological remodeling. Their activity is regulated by tissue inhibitors of matrix metalloproteinases (TIMPs). Excess MMPs and myeloperoxidase (MPO) activity has been associated with loss of tooth supporting tissues in periodontal disease (PD). We investigate the changes in salivary MMP-8, MMP-9, TIMP-1, TIMP-2, and MPO concentrations during PD treatment and compare results with plasma levels. METHODS: MMP-8, MMP-9, TIMP-1 and TIMP-2 were analyzed by ELISA. Gelatinolytic activity of MMP-9 forms were determined by zymography, and the MPO activity was determined by colorimetric assay. RESULTS: Subjects were divided into 2 groups: PD and control, which were further divided into 2 subgroups each, namely PD before (PB) and after 3months (PA) of non-surgical periodontal therapy, and healthy volunteers at baseline (CB) and 3months after baseline (CA). Subgroup PA presented lower gelatinolytic activity and MMP-8 and TIMP-2 concentrations in the saliva compared with PB (p<0.05). MPO activity was higher in PB compared with CB (p<0.05). There were significant correlations between the gelatinolytic activity of the saliva and MMP-8 and MMP-9 plasma levels. There was significant correlation between plasma and saliva TIMP-2 levels. CONCLUSION: These results suggest attenuation of some inflammatory markers in the saliva and plasma after PD treatment. Moreover, correlations between salivary and plasma levels exist for some of these markers.
    Clinica chimica acta; international journal of clinical chemistry 03/2013; 421. DOI:10.1016/j.cca.2013.03.008 · 2.76 Impact Factor
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    • "Recently, salivary diagnostics have offered promising panels of biomarkers for monitoring disease progression (Taba et al. 2005). Composite risk assessment incorporating clinical, biochemical (serum and saliva derived), as well as microbiological risk factors can characterize patient signatures predicting disease progression or stability (Kinney et al. 2011). "
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    ABSTRACT: OBJECTIVE: Regulators of peri-implant bone loss in patients with diabetes appear to involve multiple risk factors that have not been clearly elucidated. This study was conducted to explore putative local etiologic factors on implant bone loss in relation to type 2 diabetes mellitus, including clinical, microbial, salivary biomarker, and psychosocial factors. MATERIALS AND METHODS: Thirty-two subjects (divided into type 2 diabetes mellitus and non-diabetic controls), having at least one functional implant and six teeth, were enrolled in a 1-year longitudinal investigation. Analyses of clinical measurements and standardized intra-oral radiographs, saliva and serum biomarkers (via protein arrays for 20 selected markers), and plaque biofilm (via qPCR for eight periodontal pathogens) were performed at baseline and 1 year. In addition, the subjects were asked to respond to questionnaires to assess behavioral and psychosocial variables. RESULTS: There was a significant increase from baseline to 1 year in the probing depth of implants in the diabetes group (1.95 mm to 2.35 mm, P = 0.015). The average radiographic bone loss during the study period marginally increased at dental implants compared to natural teeth over the study period (0.08 mm vs. 0.05 mm; P = 0.043). The control group harbored higher levels of Treponema denticola at their teeth at baseline (P = 0.046), and the levels of the pathogen increased significantly over time around the implants of the same group (P = 0.003). Salivary osteoprotegerin (OPG) levels were higher in the diabetes group than the control group at baseline only; in addition, the salivary levels of IL-4, IL-10, and OPG associated with host defense were significantly reduced in the diabetes group (P = 0.010, P = 0.019, and P = 0.024), while controls showed an increase in the salivary OPG levels (P = 0.005). For psychosocial factors, there were not many significant changes over the observation period, except for some findings related to coping behaviors at baseline. CONCLUSIONS: The study suggests that the clinical, microbiological, salivary biomarker, and psychosocial profiles of dental implant patients with type 2 diabetes who are under good metabolic control and regular maintenance care are very similar to those of non-diabetic individuals. Future studies are warranted to validate the findings in longer-term and larger clinical trials ( # NCT00933491).
    Clinical Oral Implants Research 02/2013; DOI:10.1111/clr.12139 · 3.12 Impact Factor
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    • "Recently, Kinney et al. reported that IL-1b and MMP-8 strongly correlated with disease status of periodontitis (Kinney et al. 2011). Furthermore, increased levels of IL-1b and MMP-8 in GCF have also been associated with increased odds for subsequent attachment loss during periodontal maintenance (Reinhardt et al. 2010). "
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    ABSTRACT: AIM: Saliva is a useful diagnostic fluid for oral-related diseases. Monitoring salivary biomarkers for oral and systemic diseases could become an important complement to clinical examinations in epidemiological surveys. Recent findings indicate that it is possible to detect biomarkers for oral diseases within saliva samples. The aim of this study was to investigate if known salivary biomarkers could be used for epidemiological studies for detection of periodontitis. MATERIALS AND METHODS: A randomly selected sample of adults (20-89 years) living in Southern Sweden were invited to participate. Four hundred and fifty-one individuals were examined clinically using standard examination procedures. Stimulated saliva samples were collected and analysed for concentrations of IL-1β, -6, -8, lysozyme, matrix metalloproteinases (MMP)-8 and tissue inhibitor of metalloproteinase (TIMP)-1 using ELISA, immunofluorometric assay or Luminex assays. RESULTS: Patients with severe periodontitis presented with elevated salivary concentrations of IL-1β (p < 0.001) and MMP-8 (p < 0.001). In addition, the MMP-8/TIMP-1 ratio was significantly higher in the severe periodontitis group (p < 0.001). Smokers compared with non-smokers showed slightly lower concentrations of IL-8 (p < 0.05) and MMP-8 (p = 0.052). CONCLUSION: This investigation shows that IL-1β, MMP-8 and the ratio of MMP-8/TIMP-1 could be used as markers of periodontal disease in larger patient populations.
    Journal Of Clinical Periodontology 10/2012; 40(2). DOI:10.1111/jcpe.12038 · 3.61 Impact Factor
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