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Analysis of Molecular and Biological Basis of Systemic Effects Provoked by Periodontal Diseases

牙周病引起的系统效应的分子和生物学基础分析

基本信息

批准号：
16390611
负责人：
SHIMAUCHI Hidetoshi
金额：
$ 9.22万
依托单位：
Tohoku university
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

The purpose of this study is to explore the unidentified "missing link" to connect the relationship between periodontal and systemic diseases by molecular biological approaches. For this purpose, we focused on the most potent pathogen of chronic periodontitis, Porphyromonas gingivalis and its components, and analyzed the molecular basis of exerting virulence of this bacterium on both periodontal lesions and bodies in vivo and in vitro. Using in vivo animal models, we investigated a series of studies clarifying ; 1)the role of P.gingivalis infection on hyperlipidemia in periodontitis patients ; 2)the effect of P.gingivalis virulence factors on production of adipocytokines from adipose tissues ; 3)the molecular effects of type 2 diabetes on the healing process of periodontium. First, our in vitro study revealed that P.gingivalis LPS and fimbriae preferentially induced a unique dendritic cell subset with a weak immunostimulatory activity via TLR2-mediated signaling, finally contributing t … More o the immune escape of this bacterium in the periodontal lesion. Furthermore, in vivo studies indicated that infection of P.gingivalis is essential for up-regulation of serum triglycerides and its LPS down-regulated the serum level of adiponectin, suggesting P.gingivalis could exert its virulence after invasion into the systemic circulation. The concept of metabolic syndrome (MetS) has been evolving, that is a clustering of simple clinical measures including waist circumferences, blood pressure, triglycerides, high-density lipoproteins and glucose. This clustering appears depend on two major factors: excess body fat and metabolic susceptibility. Taken our results into this concept, invaded P.gingivalis may work as a MetS risk factor in periodontitis patients via down-regulating the serum adiponectin level. The increased risk of MetS possibly started the sequential of "Metaboic Domino" that increasing the susceptibility to diabetes and coronary heart diseases. Diabetes can delay the healing process of periodontally diseased tissue that may increase the chance of P.gigivalis invasion. In conclusion, P.gingivalis may have an adaptation system by dealing with the local immune defense that finally contributes to systemic-periodontal connection. Less

本研究的目的是通过分子生物学方法探索牙周疾病与系统性疾病之间联系的未知“缺失环节”。为此，我们重点研究了慢性牙周炎最强的致病菌牙龈卟啉单胞菌及其组成成分，并分析了该细菌在体内、外对牙周病变和机体产生毒力的分子基础。利用活体动物模型，我们进行了一系列研究，阐明了：1)牙周炎患者高脂血症中牙龈假单胞菌感染的作用；2)牙龈假单胞菌毒力因子对脂肪组织产生脂肪细胞因子的影响；3)2型糖尿病对牙周组织愈合过程的分子作用。首先，我们的体外研究表明，牙龈假单胞菌和菌毛通过tl2介导的信号优先诱导具有弱免疫刺激活性的独特的树突状细胞亚群，最终促成t…。更多的这种细菌在牙周病变中的免疫逃逸。此外，体内研究表明，牙龈假单胞菌的感染是上调血清甘油三酯和下调血清脂联素水平所必需的，提示牙龈假单胞菌可能在入侵体循环后发挥毒力。代谢综合征(METS)的概念一直在演变，即一组简单的临床指标，包括腰围、血压、甘油三酯、高密度脂蛋白和血糖。这种聚集现象取决于两个主要因素：过多的体脂和代谢易感性。将我们的结果纳入这一概念，可能通过下调血清脂联素水平作为牙周炎患者METS的危险因素。METS风险的增加可能开启了“代谢多米诺骨牌”的序幕，增加了糖尿病和冠心病的易感性。糖尿病会推迟牙周病变组织的愈合过程，这可能会增加长春新城疫杆菌侵袭的机会。综上所述，牙龈假单胞菌可能通过处理局部免疫防御而产生一种适应系统，最终促进全身-牙周连接。较少