Characterization of synovial cell clones isolated from rheumatoid arthritis patients: Possible involvement of TNF-α 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-α 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-α induced apoptosis of SYM-1 cells within 24 h and decreased OPG levels, while infliximab, a chimerical form of the anti-TNF-α antibody drug, suppressed the apoptosis and restored OPG levels. These results suggest the existence of fibroblastic cells producing OPG in the synovium, while TNF-α suppresses OPG production by inducing apoptosis in those cells. Further, infliximab is considered to inhibit bone destruction through restoration of OPG levels in RA.