维生素D结合蛋白与侵袭性牙周炎的关系及在免疫炎症中的作用

Vitamin D binding protein(DBP) is the main carrier of vitamin D metabolites. Recent studies have shown that DBP plays key roles in the innate immunity as well as endotoxin neutralization and bone metabolism. DBP gene polymorphisms at rs4588 and rs7041 influence both the structure and function of DBP. Our group first reported that 25OHD3 levels of gingival crevicular fluid(GCF) and plasma in aggressive periodontitis(AgP) patients were significantly higher than those in healthy controls, and closely related to periodontal inflammatory status. In further study, we successfully detected metabolic enzymes' expression could be regulated by inflammatory cytokines. Our preliminary experiments found that DBP levels of plasm was significantly higher in AgP patients than that in healthy controls, but was still 40 times lower than that in GCF. Besides, DBP receptor's expression in peirodontal soft tissues was detected. Thus, a hypothesis is suggested that DBP may be partly from local resources, and play dual effects in initiating and progressing of periodontitis: one for vitamin D transportation and the other for immunity and inflammation regulation. To prove the hypothesis, we are going to analyze the relationship between DBP gene polymorphisms and AgP, detect the expression and location of DBP and its receptors in periodontal tissues, explore the roles of DBP in the growth and function of peripheral blood mononuclear cells(PBMCs), and the influence on Pg-LPS's effects on apoptosis and osteogenesis of PDLCs with the possible signaling mechanisms, therefore to disclose the multi-roles of DBP play in the pathogenesis of periodontitis.

维生素D结合蛋白（DBP）是体内维生素D的主要运输蛋白，最新研究显示DBP是先天免疫的重要调控因子，在清除内毒素和骨代谢方面也发挥重要作用，其基因位点rs4588和rs7041多态性显著影响DBP蛋白结构和功能。本课题组最早发现侵袭性牙周炎（AgP）患者体液25羟维生素D3水平与牙周炎症密切相关，并在牙周膜细胞（PDLC）中检测到其代谢酶，酶表达受炎症因子调控。预实验发现AgP患者血浆DBP水平显著升高，龈沟液水平是血浆的40倍，且在牙周软组织检测出DBP受体，由此推测DBP可能有局部来源，在牙周炎发生发展中具有运输维生素D和参与免疫炎症的双重作用。课题拟系统研究DBP基因多态性与AgP的关系，验证DBP及受体在牙周组织的表达与定位，观察DBP对外周血单个核细胞生长和功能的影响，探讨DBP对Pg-LPS诱导PDLC凋亡、抑制成骨的影响及相关信号机制，全面揭示DBP在牙周炎发病机制中的作用。

维生素 D 结合蛋白(DBP)是体内维生素 D 的主要运输蛋白,最新研究显示 DBP 是先天免疫的重要调控因子,在清除内毒素和骨代谢方面也发挥重要作用,其基因位点 rs4588 和 rs7041 多态性显著影响DBP蛋白结构和功能。本研究发现，AgP患者血浆中DBP的水平显著高于健康对照者，线性回归分析显示血浆DBP水平与AgP显著相关。本研究在病例对照研究中发现DBP rs17467825位点SNP与侵袭性牙周炎的易感性相关，携带有A等位基因的个体发生AgP的风险是未携带者的两倍；该位点也与AgP患者非手术治疗的短期疗效相关。进一步发现DBP在体外培养的人牙髓和牙周组织细胞中表达；并通过组织学验证DBP在牙周组织中表达与定位，由此推测 DBP可能有局部来源,在牙周炎发生发展中具有运输维生素D和参与免疫炎症的双重作用。