Molecular aspects of the pathogenesis of periodontitis

Abstract

The past decade of basic research in periodontology has driven radical changes in our understanding and perceptions of the pathogenic processes that drive periodontal tissue destruction. The core elements of the classical model of disease pathogenesis, developed by Page & Kornman in 1997, remain pertinent today; however, our understanding of the dynamic interactions between the various microbial and host factors has changed significantly. The molecular era has unraveled aspects of genetics, epigenetics, lifestyle and environmental factors that, in combination, influence biofilm composition and the host's inflammatory immune response, creating a heterogenic biological phenotype that we label as 'periodontitis'. In this volume of Periodontology 2000, experts in their respective fields discuss these emerging concepts, such as a health-promoting biofilm being essential for periodontal stability, involving a true symbiosis between resident microbial species and each other and also with the host response to that biofilm. Rather like the gut microbiome, changes in the local environment, which may include inflammatory response mediators or viruses, conspire to drive dysbiosis and create a biofilm that supports pathogenic species capable of propagating disease. The host response is now recognized as the major contributor to periodontal tissue damage in what becomes a dysfunctional, poorly targeted and nonresolving inflammation that only serves to nourish and sustain the dysbiosis. The role of epithelial cells in signaling to the immune system is becoming clearer, as is the role of dendritic cells as transporters of periodontal pathogens to distant sites within the body, namely metastatic infection. The involvement of nontraditional immune cells, such as natural killer cells, is being recognized, and the simple balance between T-helper 1- and T-helper 2-type T-cell populations has become less clear with the emergence of T-regulatory cells, T-helper 17 cells and follicular helper cells. The dominance of the neutrophil has emerged, not only as a potential destructor when poorly regulated but as an equally unpredictable effector cell for specific B-cell immunity. The latter has emerged, in part, from the realization that neutrophils live for 5.4 days in the circulation, rather than for 24 h, and are also schizophrenic in nature, being powerful synthesizers of proinflammatory cytokines but also responding to prostaglandin signals to trigger a switch to a pro-resolving phenotype that appears capable of regenerating the structure and function of healthy tissue. Key to these outcomes are the molecular signaling pathways that dominate at any one time, but even these are influenced by microRNAs capable of 'silencing' certain inflammatory genes. This volume of Periodontology 2000 tries to draw these complex new learnings into a contemporary model of disease pathogenesis, in which inflammation and dysbiosis impact upon whether the outcome is driven toward acute resolution and stability, chronic resolution and repair, or failed resolu...

A Review on Models of Pathogenesis in Periodontitis.

“…10 The quest to identify specific periodontal pathogens has led to significant progress, including the identification of a number of candidates, mostly gram-negative anaerobic bacteria that colonize subgingival tooth sites. Foremost amongst this group are three species which comprise the so-called "red complex", are frequently isolated together, and are strongly associated with diseased sites in the mouth: Porphyromonas gingivalis (formerly known as 1118 Bacteroides gingivalis) 11 , Treponema denticola and Tannerella forsythia 13,14 . Much research work has been directed towards understanding the pathogenic mechanisms and virulence determinants of these three bacterial species in the context of a conventional host-pathogen interaction, as exemplified by diseases with a single infective etiology 13 .…”

“…11,13 Indeed, co-culture of P. gingivalis with T. denticola induces an alteration in P. gingivalis hemin uptake strategies and changes in the abundance of enzymes involved in glutamate and glycine catabolism 21 . P. gingivalis can provide a source of free glycine and isobutyric acid for T. denticola growth, while T. denticola produces succinic acid which enhances growth of P. gingivalis.…”

Contribution of Multi ‘-OMICS’ to the Future of Oral Health

“…Progression of PDs in the presence of virusinduced infection is dependent on the immune competency of the host and the local inflammatory response to typical and atypical subgingival microorganisms [13]. PDs may participate in the wound healing process and tissue destruction via the inflammatory process and various dental plaque biofilm periodonto pathogens induce different cytokine response profiles in gingival epithelial cells that may reflect their particular virulence or commensal status.…”

The role of kinases and phosphatases in the pathobiology of porphyromonas gingivalis.

“…Periodontal inflammation is not only a means by which host tissues are destroyed, rather it also functions as a means by which the periodontal bacteria can derive a wealth of nutrients important for their survival and persistence. It is this type of damage that culminates in the periodontitis phenotype characterized by a heightened and chronic inflammatory response that remains unresolved [165].…”