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

目标。在本研究中，在类风湿关节炎患者的骨吸收区域可见基质金属蛋白酶(MMPs)。该区域有大量的破骨细胞，尤其是RA关节。目的：检测抗人Fas单抗在体外和体内对类风湿关节炎(RA)破骨细胞生成的抑制作用。方法：研究方法。在体外分析中，来自外周血单个核细胞的活化的CD4()T细胞不被处理，或被人源化的抗人Fas单抗处理并与人单核细胞共培养。第12天计数抗酒石酸酸性磷酸酶(TRAP)阳性多核细胞数。为了进行活体分析，将人RA血管环组织植入SCID小鼠背部皮下的牙本质切片(SCID-HuRAg-PIT模型)。抗人Fas单抗静脉注射，每周1次，连续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CD4()T细胞与外周血单核细胞共培养诱导破骨细胞生成。用抗人Fas单抗处理活化的CD4()T细胞后，TRAP阳性的多核细胞数减少。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，在该模型中，用抗人Fas单抗处理后，种植牙本质切片上形成的凹坑数量显著减少，种植的RA滑膜组织中的淋巴细胞数量显著减少。结论。这是首次证实抗人Fas单抗通过诱导T细胞凋亡来抑制RA滑膜组织中破骨细胞的生成。从抑制炎症和骨破坏的角度来看，诱导浸润性淋巴细胞的凋亡可能是治疗类风湿关节炎的有效策略。

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.