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

本研究的目的是通过分子生物学的方法来探索牙周病与全身性疾病之间的关系中尚未确定的“缺失环节”。为此，我们重点研究了慢性牙周炎的最强病原菌牙龈卟啉单胞菌及其组分，并分析了该细菌在体内和体外对牙周病变和机体产生毒力的分子基础。本研究采用动物模型，对牙龈卟啉单胞菌感染在牙周炎患者高脂血症中的作用、牙龈卟啉单胞菌毒力因子对脂肪组织中脂肪细胞因子产生的影响、2型糖尿病对牙周组织愈合过程的分子效应进行了研究。首先，我们的体外研究表明，牙龈卟啉单胞菌LPS和菌毛通过TLR2介导的信号传导优先诱导具有弱免疫刺激活性的独特树突状细胞亚群，最终导致了牙龈卟啉单胞菌LPS和菌毛的免疫抑制作用。 ...更多信息 牙周病损中这种细菌的免疫逃逸。体内研究表明，牙龈卟啉单胞菌感染后血清甘油三酯水平升高，脂联素水平下降，提示牙龈卟啉单胞菌侵入体循环后可发挥毒力。代谢综合征（MetS）的概念一直在发展，它是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。这种聚集似乎取决于两个主要因素：多余的身体脂肪和代谢敏感性。因此，侵入性牙龈卟啉单胞菌可能通过下调血清脂联素水平而成为牙周炎患者MetS的危险因素。代谢综合征风险的增加可能启动了代谢多米诺骨牌效应，增加糖尿病和冠心病的易感性。糖尿病可延迟牙周病变组织的愈合过程，这可能会增加长臂猿侵袭的机会。总之，牙龈卟啉单胞菌可能有一个适应系统，通过处理局部免疫防御，最终有助于系统牙周连接。少

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