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

目标。在我们的研究中，在类风湿关节炎患者的骨吸收区发现基质金属蛋白酶（MMPs）。在这个区域有大量的破骨细胞，特别是在类风湿性关节炎关节。目的探讨抗人Fas单克隆抗体（mAb）对类风湿关节炎（RA）破骨细胞生成的体外和体内抑制作用。方法。对于体外分析，来自外周血单核细胞的活化CD4(+) T细胞不进行处理，或者用人源化的抗人Fas mAb处理，并与人单核细胞共培养。第12天，计数抗酒石酸磷酸酶（TRAP）阳性的多核细胞数量。为了进行体内分析，将取自人类风湿性关节炎的组织植入SCID小鼠背部皮下的牙本质切片（SCID- hurag -pit模型）。每周一次静脉滴注抗人Fas单抗，连续3周。取出移植组织和牙本质切片，分析牙本质切片上形成的凹痕。结果。在体外，活化CD4 (+) T细胞和外周单核细胞共培养诱导破骨细胞发生。活化的CD4(+) T细胞用抗人Fas单抗处理后，trap阳性的多核细胞数量减少。我们建立了一种新的监测破骨细胞发生的动物模型SCID-HuRAg-pit。我们发现，在抗人Fas mAb处理下，该模型中植入的牙本质切片上形成的凹坑数量明显减少，植入的RA滑膜组织中淋巴细胞数量明显减少。结论。这是第一个证明抗人Fas mAb通过诱导T细胞凋亡抑制RA滑膜组织破骨细胞生成的研究。在抑制炎症和骨破坏方面，诱导浸润淋巴细胞凋亡可能是一种有用的治疗RA的策略。

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.