Characterization of synovial cell clones isolated from rheumatoid arthritis patients: possible involvement of TNF-alpha in reduction of osteoprotegerin in synovium.
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.
Zhao
Baohong
B
Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan.
Takami
Masamichi
M
Miyamoto
Yoichi
Y
Suzawa
Tetsuo
T
Yamada
Atsushi
A
Mochizuki
Ayako
A
Yasuhara
Rika
R
Wang
Xiaogu
X
Inoue
Tomio
T
Namiki
Osamu
O
Sakamoto
Keizo
K
Kamijo
Ryutaro
R
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018501:Antirheumatic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D053244:Osteoprotegerin / Q000378:metabolism*; D053245:RANK Ligand / Q000096:biosynthesis; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab