The development for disrase model with periodontitis induced by Cytolethal Distending lbxin derived periodontal pathogens, and application of the model to periodontitis prevention

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It is implied that major cause of tooth loss would be periodontitis in Japanese adolescents. Study on the relationship between oral condition and systemic condition in elderly people revealed that the lowest number of chewable foods were associated with higher risk of mortality than those with the ability to chew all of the 15 types of food surveyed [hazard ratio (BR) = 2.38, 95% confidence interval (95% CI) = 1.07-5.29], though other parameters including current smoking, low serum albumin, and poor physical health status were more significant.Further, reduced chewing ability of soft foods increased the risk (HR = 2.65, 95% CI = 1.20-5.87). Thses evidences suggested that chewing ability was associated with mortality in elderly and may be a predictor for survival rate. Recently, ultrasound-targeting microbubble destruction has been employed in molecular gene therapy, and a new potent nonviral gene transfer method known as 'sonoporation' has been developed. We investigated the efficiency of sonoporation toward growth inhibition of human gingival squamous carcinoma cell line, Ca9-22, in vitro and in vivo. We found that the delivery of BLM by sonoporation induced cytotoxic effect toward Ca9-22 cells in vitro. Our in vivo results showed that tumors nearly disappeared in Ca9-22 cell-implanted nude KSN/slc mice treated with a low dose of BLM followed by sonoporation during the 4-week experimental period. We previously reported that the cytolethal distending toxin B(cdtB)from Actinobacallus actinomycetemcnmitans a periodontopathic bacterium, is responsible for cell cycle arrest and apoptosis in vitro. Thus, we used sonoporation to transfect a cdtB-expressing plasmid into Ca9-22 cells and examined cell viability in vitro and in vivo. We found that an administration of cdtB-expressing plasmid followed by sonoporation-induced marked growth inhibition of Ca9-22 cells and apoptotic cells were also observed in vitro and in vivo.