Identification of Pathogen and Host‐Response Markers Correlated With Periodontal Disease

Abstract

Background Periodontitis is the major cause of tooth loss in adults and is linked to systemic illnesses, such as cardiovascular disease and stroke. The development of rapid point-of-care (POC) chair side diagnostics has the potential for the early detection of periodontal infection and progression to identify incipient disease and reduce health care costs. However, validation of effective diagnostics requires the identification and verification of biomarkers correlated with disease progression. This clinical study sought to determine the ability of putative host- and microbially derived biomarkers to identify periodontal disease status from whole saliva and plaque biofilm. Methods One hundred human subjects were equally recruited into a healthy/gingivitis group or a periodontitis population. Whole saliva was collected from all subjects and analyzed using antibody arrays to measure the levels of multiple proinflammatory cytokines and bone resorptive/turnover markers. Results Salivary biomarker data were correlated to comprehensive clinical, radiographic, and microbial plaque biofilm levels measured by quantitative polymerase chain reaction (qPCR) for the generation of models for periodontal disease identification. Significantly elevated levels of matrix metalloproteinase (MMP)-8 and -9 were found in subjects with advanced periodontitis with Random Forest importance scores of 7.1 and 5.1, respectively. The generation of receiver operating characteristic curves demonstrated that permutations of salivary biomarkers and pathogen biofilm values augmented the prediction of disease category. Multiple combinations of salivary biomarkers (especially MMP-8 and-9 and osteoprotegerin) combined with red-complex anaerobic periodontal pathogens (such as Porphyromonas gingivalis or Treponema denticola) provided highly accurate predictions of periodontal disease category. Elevated salivary MMP-8 and T. denticola biofilm levels displayed robust combinatorial characteristics in predicting periodontal disease severity (area under the curve = 0.88; odds ratio = 24.6; 95% confidence interval: 5.2 to 116.5). Conclusions Using qPCR and sensitive immunoassays, we identified host- and bacterially derived biomarkers correlated with periodontal disease. This approach offers significant potential for the discovery of biomarker signatures useful in the development of rapid POC chairside diagnostics for oral and systemic diseases. Studies are ongoing to apply this approach to the longitudinal predictions of disease activity.

The effect of type 2 diabetes mellitus and smoking on periodontal parameters and salivary matrix metalloproteinase-8 levels

“…Previous research has shown that MMP-8 is a neutrophil secreted collagenase that can be used as a marker for periodontal inflammation (11). MMP-8 is particularly active against and can decompose types I and III collagen (12). MMP-8 activity is kept under control in healthy periodontium by TIMPs.…”

Predictive modeling of gingivitis severity and susceptibility via oral microbiota

“…Although no apical migration of the junctional epithelium occurs, these tissues become erythematous and bleed upon probing. Moreover, chronic gingivitis can progress to periodontitis, an irreversible periodontal infection characterized by alveolar bone loss, attachment loss, formation of periodontal pockets and eventually tooth loss (Sheiham, 1997;Loesche, 2007;Ramseier et al, 2009). Therefore, preventive measures against gingivitis, and improved tools for prognosis and early diagnosis, are of particular clinical significance.…”

Bráquetes convencionais e autoligados: detecção de micro-organismos na saliva e in situ, avaliação de parâmetros periodontais e quantificação de citocinas no fluido crevicular

“…Existe interação entre os componentes salivares e micro-organismos, que é determinante para os primeiros passos de formação do biofilme dental (Ahn et al, 2002;Kim et al, 2007). Entretanto, estudos evidenciam que os níveis bacterianos nas superfícies dentárias são mais elevados que os níveis salivares, e a contaminação in situ deve ser avaliada (Boutaga et al, 2007;Ramseier et al, 2009;Saygun et al, 2011). Esse fato foi também observado no presente estudo, onde os níveis de S. mutans e L. casei, que são microorganismos cariogênicos, foram maiores nos bráquetes in situ que na saliva.…”

“…Estudos recentes apontam que as citocinas e as quimiocinas são a chave para a compreensão da reabsorção óssea, durante o movimento ortodôntico (Garlet et al, 2008;Andrade et al, 2009;García-López et al, 2013;Kitaura et al, 2014), e para o estudo de condições patológicas inflamatórias, como a gengivite e periodontite (Cochran, 2008;Ramseier et al, 2009). Estes mediadores podem levar à reabsorção óssea e/ou radicular (Consolaro e Consolaro, 2009;Viecilli et al, 2009;de Rossi et al, 2010;De Oliveira et al, 2014).…”

“…Em condições patológicas, como no caso das periodontites, há liberação de citocinas e quimiocinas (Garlet et al, 2008;Andrade et al, 2009;Ramseier et al, 2009;Belibasakis e Bostanci, 2012), pois os tecidos de sustentação reagem às bactérias, aos seus produtos e subprodutos, com uma resposta imunológica e inflamatória (Azuma, 2006;Armitage e Cullinan, 2010;Armitage e Robertson, 2012;), promovendo reabsorção dos tecidos mineralizados (Consolaro e Consolaro, 2009;Viecilli et al, 2009;de Rossi et al, 2010). Além disso, estas proteínas também regulam a reabsorção óssea durante o movimento ortodôntico (Garlet et al, 2008;Andrade et al, 2009).…”