Intracellulan signal : ry pathways involving bone destruction

细胞内信号:涉及骨质破坏的途径

基本信息

批准号：
12671397
负责人：
NAKAMURA Ichiro
金额：
$ 2.11万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671397/
关键词：
ostooclast RANKL RANK rheumatoid arthritis,破骨細胞数 TRAF6

项目摘要

To clarify the mechanism by which osteoclasts are formed in culture of rheumatoid synoviocytes by exploring the involvement of receptor activator of nuclear factor kappaB ligand (RANKL). RANKL expression was examined by Northern blotting in synovial tissues from 5 rheumatoid arthritis (RA) patients and tissues from patients with osteoarthritis (OA). RANKL expression and the ability of synovial fibroblasts to support osteoclastogenesis were investigated in coculture with PBMC in the presence or absence of 1, 25(OH)2D3, and soluble RANKL/ODF and osteoprotegerin (OPG) were measured by enzyme-linked immunosorbent assay. The effects of OPG on the osteoclastogenesis in the primary culture of rheumatoid synoviocytes and the coculture system were determined. Synovial fibroblasts did not induce osteoclastogenesis when separately cocultured with PBMC. Northern blotting revealed that RANKL/ODF was highly expressed in all tissues from RA and GCT patients, but not from OA or OS patients. Cultured rheumatoid synovial fibroblasts efficiently induced osteoclastogenesis in the presence of 1, 25(OH)2D3, which was accompanied by up-regulated expression of RANKL and decreased production of OPG/OCIF. Osteoclastogenesis from synoviocytes was dose-dependently inhibited by OPG. CONCLUSION : RANKL/ODF expressed on synovial fibroblasts is involved in rheumatoid bone destruction by inducing osteoclastogenesis and would therefore be a good therapeutic target.

通过探索核因子κB配体受体激活剂（RANKL）的参与，阐明类风湿滑膜细胞培养物中破骨细胞形成的机制。通过 Northern 印迹法检测 5 名类风湿性关节炎 (RA) 患者的滑膜组织和骨关节炎 (OA) 患者的组织中的 RANKL 表达。在存在或不存在 1, 25(OH)2D3 的情况下与 PBMC 共培养，研究了 RANKL 表达和滑膜成纤维细胞支持破骨细胞生成的能力，并通过酶联免疫吸附测定法测量可溶性 RANKL/ODF 和骨保护素 (OPG)。测定了OPG对类风湿滑膜细胞原代培养和共培养系统中破骨细胞生成的影响。滑膜成纤维细胞与 PBMC 单独共培养时不诱导破骨细胞生成。 Northern印迹显示RANKL/ODF在RA和GCT患者的所有组织中高表达，但在OA或OS患者中不表达。培养的类风湿滑膜成纤维细胞在 1, 25(OH)2D3 存在下有效诱导破骨细胞生成，同时伴有 RANKL 表达上调和 OPG/OCIF 产生减少。 OPG 剂量依赖性地抑制滑膜细胞的破骨细胞生成。结论：滑膜成纤维细胞上表达的 RANKL/ODF 通过诱导破骨细胞生成参与类风湿性骨质破坏，因此可能是一个良好的治疗靶点。