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Study on Oral Health Care Aiming to Maintain and Promote General Health through the Management of Periodontal Disease

片岡, 伸介 筑波大学 DOI:10.15068/0002006189

2023.01.17

概要

Periodontal disease is an infectious disease caused by oral bacteria. As the infection progresses, periodontal tissues become chronically inflamed, and the periodontal tissues that support the teeth ( gingiva, alveolar bone) are destroyed, resulting in eventual tooth loss. New therapeutic agents are needed because periodontal disease is a chronic inflammatory state caused by bacterial infection and the effects of the few antibiotics available on the market are limited. Periodontal disease might negatively affect general health. An epidemiological survey in 1990 of American Pima Indians who congenitally develop type 2 diabetes revealed a link between diabetes and periodontal disease, and since then, several epidemiological surveys have been conducted, mostly in the USA and Europe. Periodontal disease might be involved in the progression of obesity, cardiovascular, chronic respiratory, and non-communicable diseases ( NCDs) such as Alzhei mer disease. However, little is understood about the causal relationship between periodontal and other diseases and the effects of treating periodontal disease on general health.

Here, I developed a novel, non-antibiotic agent with which to treat periodont al disease and analyzed the relationship between periodontal disease and general health among Japanese adults. I also clarified the feasibility of maintaining and promoting oral health care among the Japanese population. The causative agent of periodontal disease, Porphyromonas gingivalis (P. gingivalis ), produces the cysteine proteases Arg-gingipain (Rgp) and Lys-gingipain (Kgp) that exacerbate periodontal disease through the degradation of proteins and plasma and destruction of the immune system. Therefore, inhibitors of these proteases should be an effective treatment for periodontal disease. Dual inhibitors derived from the Rgp and Kgp structures were synthesized and analyzed their biological potential. The activities of low concentrations of the inhibitors expressed as Ki were 40 and 0.27 nM for Rgp and Kgp, respectively. It was also confirmed that the organism exerts antibacterial activities by eliminating the selectivity for proteases and the pathophysiological functions of P. gingivalis . I assessed the inhibition of vascular permeability in guinea pigs and the ability to suppress periodontal inflammation in Beagle models of canine periodontal disease. I developed the first dual inhibitor of the two pathogenic enzymes produced by P. gingivalis and confirmed its value as a new therapeutic agent against periodontal disease.

To verify the epidemiological relationship between periodontal disease and general health in Japanese adults, Hitachi Ltd. collaborated with the Faculty of Dentistry at Osaka University to conduct a cross-sectional study that introduced dental examinations into the annual health checks that Japanese companies arrange for all employees. Three parties designed the research protocol, and I assumed the lead in data acquisition and analysis. After obtaining approval from the Hitachi Institutional Review Board, the program proceeded at the Hitachi Health Management Center from 2014 to 2017 and included 1,022 Hitachi employees ( male, n = 914; female, n = 108). Periodontal disease (periodontal po cket depth (PPD), occlusal force and obesity (BMI), diabetes (Hb A1c), impaired glucose tolerance ( IGT), fasting blood glucose ( FBG), chronic obstructive pulmonary disease (% FEV 1 ), atherosclerotic heart disease, and associations with smoking were analyzed, and the odds ratios (ORs) for mutual risk was calculated. It was clarified that periodontal disease might significantly exacerbate obesity ( OR: 1.42), impaired glucose tolerance (OR: 1.48), and chronic obstructive pulmonary disease (OR: 1.38). Among general health indicators, BMI (OR: 1.28), HbA1c (OR: 4.34), FBG (OR: 1.08), % FEV 1 (OR: 0.95), and smoking ( OR: 2.32) were significantly associated with periodontal disease and the possibility of its exacerbation. Therefore, I clarified the relationship betwee n periodontal and systemic diseases among Japanese adults, and that diabetes and hyperglycemic conditions might affect the bite force. I also added dental examinations, to corporate health checks and clarified the feasibility of oral health care that maintains and promotes general health through preventing and managing periodontal disease.

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