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Periodontal disease is characterized by the destruction of the hard and soft tissues comprising the periodontium. This destruction translates to a degradation of the extracellular matrices (ECM), mediated by bacterial proteases, host-derived matrix metalloproteinases (MMPs), and other proteases released by host tissues and immune cells. Bacterial pathogens interact with host tissue, triggering adverse cellular functions, including a heightened immune response, tissue destruction, and tissue migration. The oral spirochete Treponema denticola is highly associated with periodontal disease. Dentilisin, a T. denticola outer membrane protein complex, contributes to the chronic activation of pro-MMP-2 in periodontal ligament (PDL) cells and triggers increased expression levels of activators and effectors of active MMP-2 in PDL cells. Despite these advances, no mechanism for dentilisin-induced MMP-2 activation or PDL cytopathic behaviors leading to disease is known. Here, we describe a method for purification of large amounts of the dentilisin protease complex from T. denticola and demonstrate its ability to activate MMP-2, a key regulator of periodontal tissue homeostasis. The T. denticola dentilisin and MMP-2 activation model presented here may provide new insights into the dentilisin protein and identify potential therapeutic targets for further research.

Periodontal disease is a chronic multifactorial disease triggered by a complex of bacterial species. These interact with host tissues to cause the release of a broad array of pro-inflammatory cytokines, chemokines, and tissue remodelers, such as matrix metalloproteinases (MMPs), which lead to the destruction of periodontal tissues. Patients with severe forms of periodontitis are left with a persistent pro-inflammatory transcriptional profile throughout the periodontium, even after clinical intervention, leading to the destruction of teeth-supporting tissues. The oral spirochete, Treponema denticola , is consistently found at significantly elevated levels at sites with advanced periodontal disease. Of all T. denticola virulence factors that have been described, its chymotrypsin-like protease complex, also called dentilisin, has demonstrated a multitude of cytopathic effects consistent with periodontal disease pathogenesis, including alterations in cellular adhesion activity, degradation of various endogenous extracellular matrix–substrates, degradation of host chemokines and cytokines, and ectopic activation of host MMPs. Thus, the following model of T. denticola –human periodontal ligament cell interactions may provide new knowledge about the mechanisms that drive the chronicity of periodontal disease at the protein, transcriptional, and epigenetic levels, which could afford new putative therapeutic targets.

Increased age is associated with an increased prevalence of chronic inflammatory diseases and conditions. The term inflammaging has been used to describe the age-related changes to the immune response that results in a chronic and elevated inflammatory state that contributes, in part, to the increased prevalence of disease in older adults. Periodontal disease is a chronic inflammatory condition that affects the periodontium and increases in prevalence with age. To better understand the mechanisms that drive inflammaging, a broad body of research has focused on the pathological age-related changes to key cellular regulators of the immune response. This review will focus on our current understanding of how certain immune cells (neutrophils, macrophages, T cells) change with age and how such changes contribute to inflammaging and more specifically to periodontal disease.

Atherothrombosis, leading to stroke and myocardial infarction, is responsible for most of the deaths in the world. An increased risk of atherothrombotic vascular events has been reported in patients with periodontitis. Periodontitis is a chronic multifactorial inflammatory disease, which involves a dysbiotic microbiota, and leads to a progressive destruction of the tooth-supporting apparatus. Transcient periodontal pathogen blood translocation, mainly bacteremia, has been associated with the severity of gingival inflammation. The identification of periodontal bacteria within atherothrombotic plaques is challenging and unpredictable. This review aims to summarize existing molecular technics for identifying periodontal microbiota in human atherothrombotic samples. A secondary objective is to describe a protocol for the identification of Porphyromonas gingivalis from highly calcified, atherothrombotic human samples that is based on our experience in translational cardiovascular research. Compared to direct real-time PCR, our protocol based on nested PCR has increased the detection of Porphyromonas gingivalis by 22.2% with good specificity.

The use of small antimicrobial peptides or bacteriocins, like nisin, to treat cancer is a new approach that holds great promise. Nisin exemplifies this new approach because it has been used safely in humans for many years as a food preservative, and recent laboratory studies support its anti-tumor potential in head and neck cancer. Previously, we showed that nisin (2.5%, low content) has antitumor potential in head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo. The current studies explored a naturally occurring variant of nisin (nisin ZP; 95%, high content) for its antitumor effects in vitro and in vivo. Nisin ZP induced the greatest level of apoptosis in HNSCC cells compared to low content nisin. HNSCC cells treated with increasing concentrations of nisin ZP exhibited increasing levels of apoptosis and decreasing levels of cell proliferation, clonogenic capacity, and sphere formation. Nisin ZP induced apoptosis through a calpain-dependent pathway in HNSCC cells but not in human oral keratinocytes. Nisin ZP also induced apoptosis dose-dependently in human umbilical vein endothelial cells (HUVEC) with concomitant decreases in vascular sprout formation in vitro and reduced intratumoral microvessel density in vivo. Nisin ZP reduced tumorigenesis in vivo and long-term treatment with nisin ZP extended survival. In addition, nisin treated mice exhibited normal organ histology with no evidence of inflammation, fibrosis or necrosis. In summary, nisin ZP exhibits greater antitumor effects than low content nisin, and thus has the potential to serve as a novel therapeutic for HNSCC.