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

这意味着日本青少年牙齿脱落的主要原因可能是牙周炎。对老年人口腔状况与全身健康状况关系的研究表明，咀嚼食物的数量越少，死亡风险越高[危险比(BR)=2.38，95%可信区间(95%CI)=1.07~5.29]，而目前吸烟、低血清白蛋白、身体健康状况差等其他因素更为显著。此外，软性食物的咀嚼能力降低会增加风险(HR=2.65，95%CI=1.20~5.87)。这些证据表明，咀嚼能力与老年人的死亡率有关，并可能是生存率的预测因素。近年来，超声靶向微泡破坏技术已被应用于分子基因治疗，并发展了一种新的有效的非病毒基因转移方法--声孔法。我们研究了声学修饰对人牙龈鳞状细胞癌细胞系Ca9-22体外和体内生长的抑制作用。我们在体外实验中发现BLM对Ca9-22细胞具有明显的细胞毒作用。我们的体内实验结果显示，在4周的实验期内，用低剂量的博莱曼和超声治疗后，移植了Ca9-22细胞的KSN/SLC裸鼠的肿瘤几乎消失。我们先前报道了一种牙周病细菌放线杆菌的细胞致死性膨胀毒素B(CDtB)，在体外与细胞周期停滞和细胞凋亡有关。因此，我们利用声波法将表达CDtB的质粒导入Ca9-22细胞，并检测了细胞的体外和体内活性。我们发现，在体外和体内也观察到了CDtB表达载体和超声修饰对Ca9-22细胞的生长和细胞凋亡的显着抑制。

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.