权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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，牙周炎是一种以破骨细胞过度吸收牙槽骨为特征的疾病。该细菌产生称为牙龈菌蛋白酶的半胱氨酸蛋白酶，其根据其切割位点特异性分为赖氨酸特异性（Kgp）和精氨酸特异性牙龈菌蛋白酶（Rgps）。在这项研究中，我们研究了牙龈卟啉酶对破骨细胞分化的影响。在小鼠骨髓细胞和成骨细胞共培养中，Kgp能促进1α，25（OH）_2D_3诱导的多核破骨细胞的形成，而RgpB则无此作用。生理浓度（0.1 nM）的1α，25（OH）_2D_3在100 nM Kgp存在下诱导破骨细胞形成的程度与10 nM 1α，25（OH）_2D_3诱导的程度相当。Kgp还增强了由各种微生物成分包括脂多糖诱导的破骨细胞生成。Kgp与1α，25（OH）_2D_3或脂多糖联合应用也能增加牙本质切片上形成的吸收陷窝数目，表明Kgp存在下形成的破骨细胞具有骨吸收活性。Kgp增强的破骨细胞生成与共培养基中护骨素的消耗相关，并且依赖于蛋白水解活性，因为Kgp的抑制剂苄氧羰基-苯丙氨酰-赖氨酰-无环酮完全消除了Kgp诱导的破骨细胞生成。Kgp消化骨保护素，因为其重组蛋白在血清存在下易被Kgp降解。因此，Kgp并没有增加破骨细胞在骨保护素缺乏的成骨细胞和骨髓细胞的共培养。此外，过量的重组骨保护素可消除Kgp增强的破骨细胞生成。这些结果表明，骨保护素的降解是Kgp促进破骨细胞生成的机制之一。

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.

Carbonic anhydrase IX suppresses hypertrophic differentiation of chondrocytes.

碳酸酐酶 IX 抑制软骨细胞的肥大分化。

DOI：
发表时间：
2010
期刊：
影响因子：
0
作者：
Maruyama T;Miyamoto Y;Yamada A;Yamamoto G;Yoshimura K;Akiyama T;Suzawa T;Takami M;Tachikawa T;Baba K;Kamijo R
通讯作者：
Kamijo R

Monocarboxylate transporter-1 is required for cell death in mouse chondrocyte-kike ATDC5 cells exposed to interleukin-1β; via late phase activation of NF-κB and expression of phagocyte-type NADPH-oxidase

在暴露于白细胞介素-1β的小鼠软骨细胞样 ATDC5 细胞中，单羧酸转运蛋白-1 是细胞死亡所必需的，通过 NF-κB 的晚期激活和吞噬细胞型 NADPH 氧化酶的表达来实现；

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
通讯作者：
Kamijo R

The Light and Dark Side of Bisphosphonates

双膦酸盐的光明面和黑暗面