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

这意味着在日本青少年中牙齿脱落的主要原因是牙周炎。对老年人口腔状况与全身状况之间关系的研究显示，与能够咀嚼所有15种调查食物的人相比，咀嚼食物数量最少的人死亡风险更高[风险比（BR）= 2.38，95%置信区间（95% CI）= 1.07-5.29]，尽管其他参数包括目前吸烟，低血清白蛋白、身体健康状况差等危险因素更为显著，咀嚼软质食物能力下降也增加了患病风险（HR = 2.65，95% CI = 1.20-5.87）。提示咀嚼能力与老年人的死亡率有关，可能是老年人生存率的预测指标。最近，超声靶向微泡破坏已被用于分子基因治疗，并已开发出一种新的有效的非病毒基因转移方法称为“声孔效应”。我们研究了声孔效应对人牙龈鳞癌细胞株Ca 9 -22生长抑制的效率，在体外和体内。我们发现通过声孔传递BLM在体外诱导对Ca 9 -22细胞的细胞毒性作用。我们的体内实验结果表明，在4周的实验期间，用低剂量的BLM继之以声致孔处理的Ca 9 -22细胞移植的裸KSN/slc小鼠的肿瘤几乎消失。我们曾报道过一种牙周病致病菌放线杆菌的致死性膨胀毒素B（cdt B）在体外可引起细胞周期阻滞和凋亡。因此，我们使用声致穿孔将cdtB表达质粒转染到Ca 9 -22细胞中，并在体外和体内检查细胞活力。我们发现，给予cdtB表达质粒，然后声穿孔诱导的Ca 9 -22细胞的生长抑制和凋亡细胞也观察到在体外和体内。

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.