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

Study on the molecular mechanism of alveolus bone resorption induced periodontal diseases

牙槽骨吸收诱发牙周病的分子机制研究

基本信息

批准号：
16390535
负责人：
TAKAHASHI Naoyuki
金额：
$ 9.15万
依托单位：
Matsumoto Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

The research projects "Identification of the TRAF6 interacting molecules by using the two-hybrid system", "Establishments of animal models for periodontal diseases", and "Development of the treatment method for periodontal diseases using the animal models" are currently performed in our laboratory. The results of the other projects were as follows.1.Using MyD88 deficient mice and TRIF deficient mice, the RANKL expression induced by LPS and IL-1 in osteoblasts required only the MyD88 signals but not TRIF signals2.Nod2 is s involved in RANKL expression in osteoblasts induced by muramyl dipeptide (MDP), a component of peptidoglycan, as an intracellular receptor for MDP.3.PGE_2 directly acts on murine osteoclast progenitors and enhances their differentiation into osteoclasts induced by RANKL. On the other hand, when EP4 was transduced into osteoclasts, like calcitonin, PGE_2 inhibited pit-forming activity of osteoclasts through cAMP-PKA signals.4.In vitro culture systems for human osteoclast formation was established, and effects of calcitonin on human osteoclasts were examined. Both PKA- and PKC-mediated signals were required for the calcitonin-induced human osteoclast function. In addition, PGE_2 strongly inhibits the differentiation of human osteoclast progenitors into osteoclasts. PGE_2 stimulates the production of an inhibitory factor(s) by human osteoclast progenitors, and inhibits their differentiation into osteoclasts.5.Using OPG deficient mice and RANKL deficient mice, we examined osteoclast formation in ectopic bone induced by bone morphogenetic protein 2 (BMP-2). It was shown that osteoblasts provide the critical microenvironment for the action of RANKL.

本实验室目前正在进行“利用双杂交系统鉴定TRAF 6相互作用分子”、“牙周病动物模型的建立”和“利用动物模型开发牙周病治疗方法”等研究项目。其他项目的结果如下：1.利用MyD 88缺陷小鼠和TRIF缺陷小鼠，LPS和IL-1诱导成骨细胞表达RANKL仅需要MyD 88信号而不需要TRIF信号; 2. Nod 2参与了肽聚糖组分胞壁酰二肽（MDP）诱导成骨细胞表达RANKL，作为MDP的细胞内受体。3.PGE_2直接作用于小鼠破骨细胞祖细胞，并增强RANKL诱导的破骨细胞分化。另一方面，将EP 4导入破骨细胞后，与降钙素一样，PGE_2通过cAMP-PKA信号抑制破骨细胞的成孔活性。4.建立人破骨细胞体外培养体系，观察降钙素对人破骨细胞成孔活性的影响。PKA和PKC介导的信号都是降钙素诱导的人破骨细胞功能所必需的。此外，PGE_2强烈抑制人破骨细胞祖细胞向破骨细胞的分化。PGE_2刺激破骨细胞祖细胞产生抑制因子，抑制其向破骨细胞分化。5.利用OPG缺陷小鼠和RANKL缺陷小鼠，观察骨形态发生蛋白2（BMP-2）诱导的异位骨中破骨细胞的形成。结果表明，成骨细胞为RANKL的作用提供了关键的微环境。

项目成果

期刊论文数量（27）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Osteoblasts provide a suitable microenvironment for the action of receptor activator of NF-κB ligand

成骨细胞为 NF-κB 配体受体激活剂的作用提供合适的微环境

DOI：
发表时间：
2006
期刊：
Endocrinology (In Press)
影响因子：
0
作者：
Ohno-Matsui K;Ichinose S;Nakahama K;Yoshida T;Kojima A;Mochizuki M;Morita I;Yamamoto Y.
通讯作者：
Yamamoto Y.

Cyclic AMP/protein kinase A signals enhance osteoclastic differentiation through TAK1 in osteoclast precursors.

环 AMP/蛋白激酶 A 信号通过破骨细胞前体中的 TAK1 增强破骨细胞分化。

DOI：
发表时间：
2005
期刊：
J Biol Chem (in press)
影响因子：
0
作者：
Mizoguchi T et al.;Kobayashi Y et al.
通讯作者：
Kobayashi Y et al.

Nurse-like cells from patients with rheumatoid arthritis support survival of osteoclast precursors via macrophage-colony stimulating factor production.

来自类风湿性关节炎患者的护士样细胞通过巨噬细胞集落刺激因子的产生支持破骨细胞前体的存活。

DOI：
发表时间：
2005
期刊：
Arthritis Rheum 52・12
影响因子：
0
作者：
Nakamichi Y et al.;Tsukiyama K et al.;Itoh S et al.;Yamamoto Y et al.;Udagawa N et al.;Okumura S et al.;Nakamichi Y et al.;Tsukiyama K et al.;Itoh S et al.;Yamamoto Y et al.;Udagawa N et al.;Okumura S et al.;Takahashi N et al.;Yamaki M;Kobayashi Y;Kobayashi Y;Yang S;Take I;Tsuboi H
通讯作者：
Tsuboi H

Prostaglandin E_2 strongly inhibits human osteoclasts formation.

前列腺素 E_2 强烈抑制人破骨细胞的形成。

DOI：
发表时间：
2005
期刊：
Endocrinology 146・12
影响因子：
0
作者：
Tokita;K;Inoue T.;Nakamichi Y et al.;Nakamichi Y et al.;Tsukiyama K et al.;Itoh S et al.;Yamamoto Y et al.;Udagawa N et al.;Okumura S et al.;Tsukiyama K et al.;Itoh S et al.;Yamamoto Y et al.;Udagawa N et al.;Okumura S et al.;Takahashi N et al.;Okumura S et al.;Mizoguchi T;Kobayashi Y;Kobayashi Y;Yang S;Take I
通讯作者：
Take I

Prostaglandin E2 receptors EP2 and EP4 are down-regulated during differentiation of mouse osteoclasts from their precursors