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.

研究项目“使用两杂交系统鉴定TRAF6相互作用的分子”，“牙周疾病动物模型的建立”，以及“使用动物模型的牙周疾病的治疗方法的开发”目前在我们的实验室中进行。其他项目的结果如下。1。使用MyD88缺乏小鼠和TRIF缺乏小鼠，LPS诱导的RANKL表达和成骨细胞中的IL-1仅需要MyD88信号，而无需TRIF SIGNALS2.NOD2。在肽聚糖的成分穆拉米基二肽（MDP）诱导的成骨细胞中，作为MDP.3.pge_2的细胞内受体，直接作用于鼠骨骨细胞祖细胞上，并增强其分化为兰克尔诱导的骨细胞。另一方面，当将EP4转导为破骨细胞时，例如降钙素，PGE_2通过CAMP-PKA信号抑制破骨细胞的凹坑形成活性。检查。降钙素诱导的人骨细胞功能需要PKA和PKC介导的信号。另外，PGE_2强烈抑制人骨细胞祖细胞分化为破骨细胞的分化。 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）。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.

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

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.

Arthritis Research : Methods and Protocols

关节炎研究：方法和方案

DOI：
发表时间：
2005
期刊：
影响因子：
0
作者：
Sato N;et al.;Suda K et al.;Sato N et al.;Takahashi N et al.
通讯作者：
Takahashi N et al.

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