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The interaction between osteoblast and osteoclast at the bone resorption area in the patients with rheumatoid arthritis.

类风湿性关节炎患者骨吸收区成骨细胞与破骨细胞的相互作用。

基本信息

批准号：
15591598
负责人：
UZUKI Miwa
金额：
$ 1.47万
依托单位：
Iwate Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

Objective. In our study, matrix metalloproteinases (MMPs) were seen at the bone resorption area of the patients with rheumatoid arthritis. There are numerous osteoclasts in this area especially in RA joints. To examine the suppressive effect of anti-human Fas monoclonal antibody (mAb) on osteoclastogenesis in rheumatoid arthritis (RA) both in vitro and in vivo. Methods. For in vitro analysis, activated CD4(+) T cells derived from peripheral blood mononuclear cells were left untreated or were treated with humanized anti-human Fas mAb and cocultured with human monocytes. On day 12, the number of tartrateresistant acid phosphatase (TRAP)-positive multinucleated cells was counted. For in vivo analysis, tissue derived from human RA pannus was implanted with a slice of dentin subcutaneously in the backs of SCID mice (SCID-HuRAg-pit model). Anti-human Fas mAb was administered intravenously once a week for 3 weeks. The implanted tissue and dentin slice were removed, and the pits formed on the dentin slice were analyzed. Results. In vitro, coculture of activated CD4 (+) T cells and peripheral monocytes induced osteoclastogenesis. The number of TRAP-positive multinucleated cells was reduced when activated CD4(+) T cells were treated with anti-human Fas mAb. We established a new animal model for monitoring osteoclastogenesis, SCID-HuRAg-pit. We found that with anti-human Fas mAb treatment, the number of pits formed on the implanted dentin slices was significantly reduced and the number of lymphocytes in the implanted RA synovial tissue was dramatically reduced in this model. Conclusion. This is the first study to demonstrate the suppressive effect of anti-human Fas mAb on osteoclastogenesis in RA synovial tissues through the induction of T cell apoptosis. Induction of apoptosis of infiltrated lymphocytes could be a useful therapeutic strategy for RA, in terms of suppressing both inflammation and bone destruction.

Objective.在我们的研究中，基质金属蛋白酶（MMPs）在类风湿关节炎患者的骨吸收区。在这个区域有大量的破骨细胞，特别是在RA关节。研究抗人Fas单克隆抗体（mAb）对类风湿关节炎（RA）破骨细胞生成的抑制作用。方法.对于体外分析，来源于外周血单核细胞的活化的CD 4（+）T细胞未处理或用人源化抗人Fas mAb处理并与人单核细胞共培养。在第12天，计数抗酒石酸酸性磷酸酶（TRAP）阳性多核细胞的数量。对于体内分析，将源自人RA血管翳的组织与牙本质切片一起皮下植入SCID小鼠的背部（SCID-HuRAg-pit模型）。抗人Fas mAb每周静脉注射一次，持续3周。取出种植组织和牙本质切片，分析牙本质切片上形成的凹坑。结果在体外，活化的CD 4（+）T细胞和外周血单核细胞共培养诱导破骨细胞生成。当用抗人Fas mAb处理活化的CD 4（+）T细胞时，TRAP阳性多核细胞的数量减少。我们建立了一种新的监测破骨细胞生成的动物模型SCID-HuRAg-pit。我们发现，抗人Fas单克隆抗体治疗，在植入的牙本质切片上形成的凹坑的数量显着减少，在植入的RA滑膜组织中的淋巴细胞的数量显着减少在这个模型中。结论这是第一个研究证明抗人Fas单克隆抗体通过诱导T细胞凋亡对RA滑膜组织中破骨细胞生成的抑制作用。在抑制炎症和骨破坏方面，诱导浸润淋巴细胞凋亡可能是RA的一种有用的治疗策略。

项目成果

期刊论文数量（35）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

末梢CRFとurocortinの役割-免疫系

外周 CRF 和尿皮质素 - 免疫系统的作用

DOI：
发表时间：
2005
期刊：
内分泌・糖尿病科 21(5)
影响因子：
0
作者：
宇月美和;高橋和広;笹野公伸;澤井高志
通讯作者：
澤井高志

Sex steroid receptors in rheumatoid arthritis

DOI：
10.1042/cs20030317
发表时间：
2004-03-01
期刊：
CLINICAL SCIENCE
影响因子：
6
作者：
Ishizuka, M;Hatori, M;Sasano, H
通讯作者：
Sasano, H

Characterization of ANK positive cells in joint tissue from patients with calcium pyrophosphate dihydrate crystal deposition disease (CPPD).

二水焦磷酸钙晶体沉积病 (CPPD) 患者关节组织中 ANK 阳性细胞的特征。

DOI：
发表时间：
2005
期刊：
Arthritis Rheum 52・9
影响因子：
0
作者：
Uzuki M;Sawai T;Ryan LM;Rosenthal A;Masuda I
通讯作者：
Masuda I

Cell characterization of mononuclear and giant cells constituting pigmented villonodular synovitis

构成色素沉着绒毛结节性滑膜炎的单核细胞和巨细胞的细胞特征

DOI：
发表时间：
2003
期刊：
Hum Pathol 34.1
影响因子：
0
作者：
Miwa Uzuki;Mayumi Iwasaki;Yoshitaka Itoh;Shuji Ouchi;Shinichi Oikawa;Takashi Sawai;Akira Kurose;佐々木素子;黒瀬顕;Wataru Yoshida
通讯作者：
Wataru Yoshida

The dynamics of hyaluronic acid in patients with rheumatoid arthritis. -The basic research about the effectivity of high molecular weight hyaluronic acid therapy

类风湿关节炎患者透明质酸的动态变化。