Molecular Mechanisms of Interaction between Periodontitis and Cardiovascular and Bone Metabolic Disorders

牙周炎与心血管和骨代谢紊乱相互作用的分子机制

基本信息

批准号：
17209057
负责人：
NAKAYAMA Koji
金额：
$ 31.7万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17209057/
关键词：
Infectious Disease Bacteria Dental Science Circulation ・ High Blood Pressure Immunoloey 骨代謝

项目摘要

The periodontopathic bacterium Porphyromonas gingivalis has the ability to agglutinate human erythrocytes. We found that the Hgp44 domain protein, which is encoded by gingipain-related genes of P. gingivalis, can agglutinate erythrocytes by using a recombinant Hgp44 protein. The target molecule on the cell surface of erythrocytes against Hgp44 was found to be glycophorin. Also, we found that a peptide encoded by a DNA region backward of the region encoding Hgp44 has the inhibitory effect on the Hgp44-mecliated hemagglutination.P. gingivalis cell-induced platelet aggregation is particularly important for interaction between periodontal disease and cardiovascular disease. It has been believed that P. gingivalis-mediated platelet aggregation is caused by activation of PAR receptor on platelets by Arg-gingipain. However, we found that P. gingivalis cell-mediated platelet aggregation does not depend on Arg-gingipain but Hgp44 protein on the bacterial cell surface, anti-P. gingivalis antibody in serum, and FcγRIIa and GPIlb/IIIa on platelets.Alveolar bone resorption is one of the characteristic symptoms in periodontal disease, which results in tooth loss. Tooth loss causes loss of the gingival crevice that is an anatomical niche for periodontal pathogens such as P. gingivalis. We found that culture supernatants of P. gingivalis have the ability to inhibit in vitro osteoclastogenesis from bone marrow macrophages and determined that a hemoglobin receptor protein (HbR), which is a major protein in the culture supernatants, is the inhibitor to osteoclast formation. The HbR protein inhibited RANKL-induced Akt phosphorylation and expression of NFATc1 and c-Fos.

牙周病细菌牙龈卟啉单胞菌具有凝集人类红细胞的能力，我们发现由牙龈卟啉单胞菌的牙龈蛋白酶相关基因编码的Hgp44结构域蛋白可以通过利用重组的Hgp44蛋白来凝集红细胞上的目标分子。发现红细胞表面对抗 Hgp44此外，我们发现Hgp44编码区域后面的DNA区域编码的肽对Hgp44相关的血凝作用具有抑制作用。P.牙龈细胞诱导的血小板聚集对于牙周病和心血管疾病之间的相互作用特别重要。人们认为牙龈卟啉单胞菌介导的血小板聚集是由Arg-gingipain激活血小板上的PAR受体引起的。然而，我们发现牙龈卟啉单胞菌细胞介导的血小板聚集并不依赖于Arg-gingipain，而是依赖于细菌细胞表面的Hgp44蛋白、血清中的抗牙龈卟啉单胞菌抗体以及血小板上的FcγRIIa和GPIlb/IIIa。是牙周病的特征症状之一，它会导致牙齿脱落，导致牙龈缝隙丧失，而牙龈缝隙是牙齿的解剖学利基。我们发现牙龈卟啉单胞菌的培养上清液具有抑制骨髓巨噬细胞的体外破骨细胞生成的能力，并确定血红蛋白受体蛋白（HbR）是培养上清液中的主要蛋白质，是破骨细胞形成的抑制剂，HbR 蛋白抑制 RANKL 诱导的 Akt 磷酸化以及 NFATc1 和 c-Fos 的表达。

项目成果

期刊论文数量（67）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Gingipains inactivates a cell surface ligand on Porphyromonas gingivalls that induces TLR2- and TLR4-independent signaling.

Gingipains 使牙龈卟啉单胞菌上诱导 TLR2 和 TLR4 独立信号传导的细胞表面配体失活。

DOI：
发表时间：
期刊：
Microbiology and Immunology In press
影响因子：
0
作者：
Kondo;Y.;Yoshimura;M.;Ohara;N.;Shoji;M.;Yukitake;H.;Naito;M.;Fujiwara;T.;Nakayama;K.;Hotokezaka et al.;Fujimura et al.;Kishimoto et al.
通讯作者：
Kishimoto et al.

Temporal activation of anti-and pro-apoptotic factors in human gingival fibroblasts infected with the periodontal pathogen, Porphyromonas gingivalis : potential role of bacterial proteases in host signalling

感染牙周病原体牙龈卟啉单胞菌的人牙龈成纤维细胞中抗凋亡因子和促凋亡因子的暂时激活：细菌蛋白酶在宿主信号传导中的潜在作用

DOI：
发表时间：
2006
期刊：
BMC Microbiol
影响因子：
4.2
作者：
Urnowey;S.;Ansai;T.;Bitko;V.;Nakayama;K.;Takehara;T.;Barik;S.
通讯作者：
S.

Arginine-specific gingipains from Porphyromonas gingivalis stimulate production of hepatocyte growth factor (scatter factor) through protease-activated receptors in human gingival fibroblasts in culture.

来自牙龈卟啉单胞菌的精氨酸特异性牙龈蛋白酶通过培养的人牙龈成纤维细胞中的蛋白酶激活受体刺激肝细胞生长因子（分散因子）的产生。

DOI：
发表时间：
2005
期刊：
Journal of Immunology 175
影响因子：
0
作者：
Uehara;A.;Muramoto;K.;Imamura;T.;Nakayama;K.;Potempa;J.;Travis;J.;Sugawara;S.;Takada;H.;Uehara et al.
通讯作者：
Uehara et al.

Temporal activation of anti-and pro-apoptotic factors in human

人类抗凋亡因子和促凋亡因子的时间激活