Intracellulan signal : ry pathways involving bone destruction

点击翻译按钮获取中文摘要

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.