Loricrin and Cytokeratin Disorganisation in Severe Forms of Periodontitis.

OBJECTIVE: The aim of this research was to investigate the role of the cornified epithelium, the outermost layer of the oral mucosa, engineered to prevent water loss and microorganism invasion, in severe forms of periodontitis (stage III or IV, grade C). METHODS: Porphyromonas gingivalis, a major periodontal disease pathogen, can affect cornified epithelial protein expression through chronic activation of signal transducer and activator of transcription 6 (Stat6). We used a mouse model, Stat6VT, that mimics this to determine the effects of barrier defect on P gingivalis-induced inflammation, bone loss, and cornified epithelial protein expression, and compared histologic and immunohistologic findings with tissues obtained from human controls and patients with stage III and IV, grade C disease. Alveolar bone loss in mice was assessed using micro-computerised tomography, and soft tissue morphology was qualitatively and semi-quantitatively assessed by histologic examination for several proteins, including loricrin, filaggrin, cytokeratin 1, cytokeratin 14, a proliferation marker, a pan-leukocyte marker, as well as morphologic signs of inflammation. Relative cytokine levels were measured in mouse plasma by cytokine array. RESULTS: In the tissues from patients with periodontal disease, there were greater signs of inflammation (rete pegs, clear cells, inflammatory infiltrates) and a decrease and broadening of expression of loricrin and cytokeratin 1. Cytokeratin 14 expression was also broader and decreased in stage IV. P gingivalis-infected Stat6VT mice showed greater alveolar bone loss in 9 out of 16 examined sites, and similar patterns of disruption to human patients in expression of loricrin and cytokeratins 1 and 14. There were also increased numbers of leukocytes, decreased proliferation, and greater signs of inflammation compared with P gingivalis-infected control mice. CONCLUSIONS: Our study provides evidence that changes in epithelial organisation can exacerbate the effects of P gingivalis infection, with similarities to the most severe forms of human periodontitis.

Is There a Causal Link Between Periodontitis and Cardiovascular Disease? A Concise Review of Recent Findings.

There is substantial evidence in support of an association between periodontitis and cardiovascular disease. The most important open question related to this association is causality. This article revisits the question of causality by reviewing intervention studies and systematic reviews and meta analyses published in the last 3 years. Where are we now in answering this question? Whilst systematic reviews and epidemiological studies continue to support an association between the diseases, intervention studies fall short in determining causality. There is a dearth of good-quality, blinded randomised control trials with cardiovascular disease outcomes. Most studies use surrogate markers/biomarkers for endpoints, and this is problematic as they may not be reflective of cardiovascular disease status. This review further highlights another issue with surrogate markers/biomarkers: the potential for collider bias. Ethical considerations surrounding nontreatment have led to calls for a well-annotated database containing in-depth dental health data. Finally, a relatively new and important risk factor for cardiovascular disease, clonal haematopoiesis of indeterminate potential, is discussed. Clonal haematopoiesis of indeterminate potential increases cardiovascular risk by more than 40%, and inflammation is a contributing factor. The impact of periodontal disease on this emerging risk factor has yet to be explored. Although the question of causality in the association between periodontal disease and cardiovascular disease remains unanswered, the importance of good oral health in maintaining good heart health is reiterated.