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

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。

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.