A study on the mechanism of bone resorption by gingipains, the major proteases produced by Porphyromonas gingivalis

牙龈卟啉单胞菌产生的主要蛋白酶牙龈蛋白酶骨吸收机制的研究

基本信息

批准号：
21592372
负责人：
MIYAMOTO Yoichi
金额：
$ 2.83万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21592372/
关键词：
歯周病ジンジパイン破骨細胞分化細胞分化

项目摘要

Porphyromonas gingivalis is one of the major pathogens of periodontitis, a condition characterized by excessive alveolar bone resorption by osteoclasts. The bacterium produces cysteine proteases called gingipains, which are classified according to their cleavage-site specificity into lysine-specific(Kgp) and arginine-specific gingipains(Rgps). In this study, we examined the effects of gingipains on osteoclast differentiation. In co-cultures of mouse bone marrow cells and osteoblasts, formation of multinucleated osteoclasts induced by 1α, 25-dihydroxyvitamin D_3[1α, 25(OH)_2D_3] was augmented by Kgp but not by RgpB. A physiological concentration(0.1 nM) of 1α, 25(OH)_2D_3 induced the osteoclast formation in the presence of 100 nM Kgp to the extent comparable to that induced by 10 nM 1α, 25(OH)_2D_3. Kgp also enhanced osteoclastogenesis induced by various microbial components including lipopolysaccharide. Combined use of Kgp and 1α, 25(OH)_2D_3 or lipopolysaccharide also increased the number of resorption pits developed on dentin slices, indicating the osteoclasts formed in the presence of Kgp possess bone-resorbing activity. The enhanced osteoclastogenesis by Kgp was correlated with a depletion of osteoprotegerin in co-culture media and proteolytic activity-dependent, since benzyloxycarbonyl-phenylalanyl-lysyl-acycloxyketone, an inhibitor of Kgp, completely abolished osteoclastogenesis induced by Kgp. Kgp digested osteoprotegerin, since its recombinant protein was susceptible to degradation by Kgp in the presence of serum. As a result, Kgp did not augment osteoclastogenesis in co-cultures of osteoprotegerin-deficient osteoblasts and bone marrow cells. In addition, enhanced osteoclastogenesis by Kgp was abolished by excess amount of recombinant osteoprotegerin. These findings suggest that degradation of osteoprotegerin is one of the mechanisms underlying promotion of osteoclastogenesis by Kgp.

牙龈卟啉单胞菌是牙周炎的主要病原体之一，这种疾病是由破骨细胞分辨出过多的牙槽骨骨骼的特征。该细菌会产生称为gingipairins的半胱氨酸蛋白，这些蛋白根据其裂解位点特异性分类为赖氨酸特异性（KGP）和精氨酸特异性金刚蛋白（RGP）。在这项研究中，我们检查了金格林蛋白对破骨细胞分化的影响。在小鼠骨髓细胞和成骨细胞的共培养中，由1α，25-二羟基维生素D_3 [1α，25（OH）_2D_3]诱导的多核破骨细胞的形成被kgp增强，但不是由RGPB增强。 1α，25（OH）_2D_3的物理浓度（0.1 nm）在100 nm kgp的情况下诱导破骨细胞的形成，其程度与10 nm1α，25（OH）_2d_3诱导的范围相当。 KGP还增强了包括脂多糖在内的各种微生物成分诱导的破骨细胞生成。 KGP和1α，25（OH）_2D_3或脂多糖的联合使用也增加了在牙本质切片上开发的分辨率凹坑的数量，表明在存在KGP潜在骨骼逆性活性的情况下形成的破骨细胞。 The enhanced osteoclastogenesis by Kgp was correlated with a depletion of osteoprotegerin in co-culture media and proteolytic activity-dependent, since benzyloxycarbonyl-phenylalanyl-lysyl-acycloxyketone, an inhibitor of Kgp, completely abolished osteoclastogenesis induced by Kgp. KGP消化了骨蛋白，因为其重组蛋白容易在血清存在下KGP降解。结果，KGP并未增加骨蛋白蛋白蛋白蛋白果蛋白缺乏成骨细胞和骨髓细胞的共培养中的破骨细胞生成。另外，通过过量的重组骨蛋白蛋白消除了KGP的增强的破骨细胞生成。这些发现表明，骨蛋白蛋白蛋白蛋白的降解是kgp促进骨失骨的基础机制之一。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Monocarboxylate transporter-1 is involved in the activation of NF-κB and expression of phagocyte-type NADPH-oxidase in mouse chondrocytes exposed to interleukin-1β

单羧酸转运蛋白 1 参与暴露于白细胞介素 1β 的小鼠软骨细胞中 NF-κB 的激活和吞噬细胞型 NADPH 氧化酶的表达

DOI：
发表时间：
2009
期刊：
影响因子：
0
作者：
吉村健太郎;et al.
通讯作者：
et al.

二本鎖RNAアナログはインターフェロンβ/STAT1経路を介して破骨細胞分化を抑制し骨粗鬆症モデル動物の骨量を増加させる

双链RNA类似物通过干扰素β/STAT1途径抑制骨质疏松模型动物的破骨细胞分化并增加骨量

DOI：
发表时间：
2011
期刊：
影响因子：
0
作者：
Yoshimura K;Miyamoto Y;Yasuhara R;Maruyama T;Akiyama T;Yamada A;Takami M;Suzawa T;Tsunawaki S;Tachikawa T;Baba K;Kamijo R;Suzuki T and Inouye S;中村史朗ほか;宮本阿礼,高見正道,宮本洋一,山田篤,望月文子,井上富雄,上條竜太郎
通讯作者：
宮本阿礼,高見正道,宮本洋一,山田篤,望月文子,井上富雄,上條竜太郎

The Light and Dark Side of Bisphosphonates

双膦酸盐的光明面和黑暗面