Periodontitis is a chronic inflammatory condition of the periodontium involving interactions between bacterial products, numerous cell populations and inflammatory mediators. It is generally accepted that periodontitis is initiated by complex and diverse microbial biofilms which form on the teeth, i.e. dental plaque. Substances released from this biofilm such as lipopolysaccharides, antigens and other virulence factors, gain access to the gingival tissue and initiate an inflammatory and immune response, leading to the activation of host defence cells. As a result of cellular activation, inflammatory mediators, including cytokines, chemokines, arachidonic acid metabolites and proteolytic enzymes collectively contribute to tissue destruction and bone resorption. This review summarises recent studies on the pathogenesis of periodontitis, with the main focus on inflammatory mediators and their role in periodontal disease.

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Inflammatory mediators in the pathogenesis of periodontitis

Matrix metalloproteinase-8 is a promising candidate biomarker for oral fluid (gingival crevicular fluid, peri-implant sulcular fluid and saliva) and mouthrinse chair-side/point-of-care diagnostics to predict, diagnose and determine the progressive phases of episodic periodontitis and peri-implantitis, as well as to monitor the treatments and medications. Matrix metalloproteinase-8 can be used alone or together with interleukin-1beta and Porphyromonas gingivalis to calculate cumulative risk score at the subject level as a successful diagnostic tool, especially in large-scale public health surveys, in which a thorough periodontal examination is not feasible.

Analysis of matrix metalloproteinases, especially MMP-8, in gingival creviclular fluid, mouthrinse and saliva for monitoring periodontal diseases.

Epidemiologic and cancer control studies on the association of periodontal disease and cancer risk mostly suggest a positive association with overall cancer risk and certain specific types of cancer. These findings are generally consistent among cross-sectional and longitudinal studies. In this paper, we review epidemiologic studies and current knowledge on periodontal disease and cancer, with a focus on those studies conducted in the years following the Joint European Federation of Periodontology/American Academy of Periodontology Workshop on "Periodontitis and Systemic Diseases" in November 2012. This review also explores the role of chronic inflammation as a biologically plausible mechanistic link between periodontal disease and risk of cancer. Furthermore, it highlights studies that have examined the potential importance of certain periodontal pathogens in this association.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/prd.12329

Periodontal disease and cancer: Epidemiologic studies and possible mechanisms.

https://pure.uva.nl/ws/files/2691688/173286_Loos_Genetic_associations_in_periodontitis_DCNA.pdf

What is the Contribution of Genetics to Periodontal Risk

Here we report an in-silico approach for identification, characterization and validation of deleterious non-synonymous SNPs (nsSNPs) in the interleukin-8 gene using three steps. In first step, sequence homology-based genetic analysis of a set of 50 coding SNPs associated with 41 rsIDs using SIFT (Sorting Intolerant from Tolerant) and PROVEAN (Protein Variation Effect Analyzer) identified 23 nsSNPs to be putatively damaging/deleterious in at least one of the two tools used. Subsequently, structure-homology based PolyPhen-2 (Polymorphism Phenotyping) analysis predicted 9 of 23 nsSNPs (K4T, E31A, E31K, S41Y, I55N, P59L, P59S, L70P and V88D) to be damaging. According to the conditional hypothesis for the study, only nsSNPs that score damaging/deleterious prediction in both sequence and structural homology-based approach will be considered as 'high-confidence' nsSNPs. In step 2, based on conservation of amino acid residues, stability analysis, structural superimposition, RSMD and docking analysis, the possible structural-functional relationship was ascertained for high-confidence nsSNPs. Finally, in a separate analysis (step 3), the IL-8 deregulation has also appeared to be an important prognostic marker for detection of patients with gastric and lung cancer. This study, for the first time, provided in-depth insights on the effects of amino acid substitutions on IL-8 protein structure, function and disease association.

/pdf/predicting-the-functional-consequences-of-non-synonymous-m163ephss7.pdf

Predicting the functional consequences of non-synonymous single nucleotide polymorphisms in IL8 gene.

Association of matrix metalloproteinase (MMP)-1, 3, 9, interleukin (IL)-2, 8 and cyclooxygenase (COX)-2 gene polymorphisms with chronic periodontitis in a Chinese population.

A complex network of chemokines and pro- and anti-inflammatory mediators is involved in the initiation and progression of chronic periodontitis. Matrix metalloproteinases (MMPs), the main enzymes responsible for matrix degradation, are important for periodontal tissue destruction, but their activity can be inhibited by tissue inhibitors of metalloproteinases (TIMPs). Interleukin-12 (IL-12) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been shown to be involved in inflammatory and autoimmune diseases. Until now, no studies have reported on serum levels of MMP-2 and GM-CSF in chronic periodontitis patients and periodontally healthy subjects. Therefore, the aim of the present study was to determine the serum levels of MMP-2, TIMP-1, IL-12 and GM-CSF in chronic periodontitis patients, compared with periodontally healthy subjects. The test group of the study comprised 40 chronic periodontitis patients, whereas the control group included 108 periodontally healthy individuals. Blood samples were collected from all participants and examined using enzymelinked immunosorbent assay (ELISA) analysis. Clinical periodontal parameters (bleeding on probing, clinical attachment level and probing pocket depth) and the serum levels of MMP-2, TIMP-1, IL-12 and GM-CSF were statistically significantly higher in the test group than in the conptrol group. These results may indicate that MMP-2, TIMP-1, IL-12 and GM-CSF could be involved in the initiation and progression of chronic periodontitis. Key words : Chronic periodontitis, cytokines, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-1 (TIMP-1), interleukin-12 (IL-12), granulocyte–macrophage colony-stimulating factor (GMCSF).

/pdf/the-effect-of-chronic-periodontitis-on-serum-levels-of-jtpybkr9pm.pdf

The effect of chronic periodontitis on serum levels of matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-1 (TIMP-1), interleukin-12 (IL-12) and granulocyte-macrophage colony-stimulating factor (GM-CSF)

Peixi Liao

Papers

Association of matrix metalloproteinase (MMP)-1, 3, 9, interleukin (IL)-2, 8 and cyclooxygenase (COX)-2 gene polymorphisms with chronic periodontitis in a Chinese population.

The effect of chronic periodontitis on serum levels of matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-1 (TIMP-1), interleukin-12 (IL-12) and granulocyte-macrophage colony-stimulating factor (GM-CSF)