Prevention of alveolar bone resorption and athrosclerosis through the regulation of OPG gene expression

通过调节 OPG 基因表达预防牙槽骨吸收和动脉硬化

• 批准号: 18592258
• 负责人: NAGASAWA Toshiyuki
• 金额: $ 2.47万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18592258/
• 关键词: OPG; RANKL; atherosclerosis; P. gingivalis; 歯周病原細菌; 血管平滑筋細胞; 歯肉線維芽細胞; 歯根膜線維芽細胞

Chronic inflammation and infection play pivotal roles in the pathogenesis of abdominal aortic aneurysm (AAA). Receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) have recently been implicated as key partners of osteoimmunology and vascular diseases. Although periodontopathic bacteria were detected in AAA specimens, the role of periodontal infection in AAA pathogenesis remains unclear. This study investigated the association of periodontopathic bacteria with the expression of RANKL and OPG in AAA.AAA and normal aorta tissues were collected from patients during surgical AAA repair. Expression of RANKL and OPG mRNA was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and localization of RANKL in AAA tissues was examined by immunohistochemistry. Periodontopathic bacteria in specimens were detected by PCR. Our results showed significantly increased RANKL, but decreased OPG, mRNA levels in AAA tissues when compared to normal aorta tissues. RANKL was localized in the intimal and medial layers and was expressed in mononuclear and vascular smooth muscle cells (VSMCs). The expression levels of RANKL, but not OPG, were positively correlated with the presence of Porphyromonas gingivalis and Treponema denticola, but not A. actinomycetemcomitans, in vessel tissues. These periodontopathic bacteria were not detected in any normal tissues. P. gingivalis lipopolysaccharide was able to upregulate RANKL expression in VSMCs. Our findings demonstrated the association between periodontopathic bacteria and RANKL upregulation in AAA, suggesting a potential role of periodontal infection in the pathogenesis of AAA, via RANKL upregulation.

慢性炎症和感染在腹主动脉瘤（AAA）的发病机制中发挥着关键作用。核因子 kappa B 配体受体激活剂 (RANKL) 和骨保护素 (OPG) 最近被认为是骨免疫学和血管疾病的关键伙伴。尽管在 AAA 标本中检测到牙周病细菌，但牙周感染在 AAA 发病机制中的作用仍不清楚。本研究调查了牙周病细菌与 AAA 中 RANKL 和 OPG 表达的关系。从 AAA 手术修复期间的患者身上收集了 AAA 和正常主动脉组织。通过逆转录聚合酶链式反应 (RT-PCR) 分析 RANKL 和 OPG mRNA 的表达，并通过免疫组织化学检查 RANKL 在 AAA 组织中的定位。通过PCR检测标本中的牙周病细菌。我们的结果显示，与正常主动脉组织相比，AAA 组织中 RANKL 显着升高，但 OPG、mRNA 水平降低。 RANKL 定位于内膜和内侧层，并在单核细胞和血管平滑肌细胞 (VSMC) 中表达。 RANKL（而非 OPG）的表达水平与血管组织中牙龈卟啉单胞菌和齿垢密螺旋体的存在呈正相关，但与伴放线放线菌无关。在任何正常组织中均未检测到这些牙周病细菌。牙龈卟啉单胞菌脂多糖能够上调 VSMC 中的 RANKL 表达。我们的研究结果证明了牙周病细菌与 AAA 中 RANKL 上调之间的关联，表明牙周感染通过 RANKL 上调在 AAA 发病机制中发挥潜在作用。

项目成果

Transforming growth factor-beta stimulates interleukin-11 production by human periodontal ligament and gingival fibroblasts.

转化生长因子-β 刺激人牙周膜和牙龈成纤维细胞产生白细胞介素 11。

• 发表时间: 2006
• 期刊: Journal of Clinical Periodontology 33(3)
• 作者: 福本敏;湯浅健司;山田亜矢;野中和明;赤坂 徹;Toshiyuki Nagasawa et al.;Reiko Yashiro et al.
• 通讯作者: Reiko Yashiro et al.

Elevated IgG titers to periodontal pathogens related to Buerger disease

• DOI: 10.1016/j.ijcard.2006.11.032
• 发表时间: 2007-10-01
• 期刊: INTERNATIONAL JOURNAL OF CARDIOLOGY
• 影响因子: 3.5
• 作者: Chen, Yi-Wen;Iwai, Takehisa;Ishikawa, Isao
• 通讯作者: Ishikawa, Isao

High incidence of actinobacillus actinomycetemcomitans infection in a cute coronary syndrome.

可爱冠状动脉综合征中伴放线杆菌感染的发生率很高。

• 发表时间: 2007
• 期刊: Int Heart J. 48
• 作者: M. Ibi;A. Ishisaki;M. Yamamoto;A. Wada;T. Kozakai;A. Nakashima;J. Iida;S. Takao;Y. Izumi;A. Yokoyama;M. Tamura,;Sakurai K
• 通讯作者: Sakurai K

Internal prostaglandin synthesis augments osteoprotegerin production in human gingival fibroblasts stimulated by lipopolysaccharide

脂多糖刺激的人牙龈成纤维细胞内部前列腺素合成增强了骨保护素的产生

• 发表时间: 2007
• 期刊: Clin Exp Immunol 149(2)
• 作者: Kiji M;Nagasawa T;Hormdee D;Yashiro R;Kobayashi H;Noguchi K;Nitta H;Izumi Y;Ishikawa I.
• 通讯作者: Ishikawa I.

Immunoglobulin G subclass antibody profiles in Porphyromonas gingivalis-associated aggressive and chronic periodontitis patients

牙龈卟啉单胞菌相关侵袭性和慢性牙周炎患者的免疫球蛋白 G 亚类抗体谱

• 发表时间: 2006
• 期刊: Oral Microbiol Immunol 21(5)
• 作者: Takeuchi;Y.;Aramaki;M.;Nagasawa;T.;Umeda;M.;Oda;S.;Ishikawa;I
• 通讯作者: I