Characterization of synovial cell clones isolated from rheumatoid arthritis patients: possible involvement of TNF-alpha in reduction of osteoprotegerin in synovium
Autor: | Osamu Namiki, Xiaogu Wang, Keizo Sakamoto, Atsushi Yamada, Tetsuo Suzawa, Tomio Inoue, Rika Yasuhara, Baohong Zhao, Ryutaro Kamijo, Masamichi Takami, Ayako Mochizuki, Yoichi Miyamoto |
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Rok vydání: | 2007 |
Předmět: |
musculoskeletal diseases
Adult Male medicine.medical_specialty Cell Survival Cellular differentiation Immunology Osteoclasts Apoptosis Biochemistry Arthritis Rheumatoid Osteoprotegerin Osteoclast Internal medicine medicine Immunology and Allergy Humans Viability assay Molecular Biology Cells Cultured Aged biology Chemistry Tumor Necrosis Factor-alpha RANK Ligand Synovial Membrane Antibodies Monoclonal Cell Differentiation Hematology Fibroblasts Middle Aged Infliximab Endocrinology medicine.anatomical_structure Synovial Cell RANKL Antirheumatic Agents biology.protein Cancer research Tumor necrosis factor alpha Female Synovial membrane |
Zdroj: | Cytokine. 41(1) |
ISSN: | 1096-0023 |
Popis: | To elucidate the role of the synovium in bone destruction by osteoclasts in rheumatoid arthritis (RA), primary synovial cells isolated from RA patients were cultured and characterized. The cultured primary cells did not produce RANKL (TRANCE/ODF/OPGL/TNFSF11/CD254), an inducer of osteoclast differentiation, but constitutively produced its inhibitor, osteoprotegerin (OPG). Addition of TNF-alpha to the primary cultures of synovial cells reduced the cell viability and strongly suppressed OPG production. We then established nine synovial cell clones, including SYM-1, responsible for OPG production from primary synovial cell cultures. TNF-alpha induced apoptosis of SYM-1 cells within 24h and decreased OPG levels, while infliximab, a chimerical form of the anti-TNF-alpha antibody drug, suppressed the apoptosis and restored OPG levels. These results suggest the existence of fibroblastic cells producing OPG in the synovium, while TNF-alpha suppresses OPG production by inducing apoptosis in those cells. Further, infliximab is considered to inhibit bone destruction through restoration of OPG levels in RA. |
Databáze: | OpenAIRE |
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