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Characterization of synovial cell clones isolated from rheumatoid arthritis patients: possible involvement of TNF-alpha in reduction of osteoprotegerin in synovium.
- Source :
-
Cytokine [Cytokine] 2008 Jan; Vol. 41 (1), pp. 61-70. Date of Electronic Publication: 2007 Dec 20. - Publication Year :
- 2008
-
Abstract
- 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.
- Subjects :
- Adult
Aged
Antibodies, Monoclonal pharmacology
Antirheumatic Agents pharmacology
Apoptosis drug effects
Arthritis, Rheumatoid pathology
Cell Differentiation drug effects
Cell Survival drug effects
Cells, Cultured
Female
Fibroblasts pathology
Humans
Infliximab
Male
Middle Aged
Osteoclasts pathology
RANK Ligand biosynthesis
Synovial Membrane pathology
Tumor Necrosis Factor-alpha metabolism
Arthritis, Rheumatoid metabolism
Fibroblasts metabolism
Osteoclasts metabolism
Osteoprotegerin metabolism
Synovial Membrane metabolism
Tumor Necrosis Factor-alpha pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0023
- Volume :
- 41
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cytokine
- Publication Type :
- Academic Journal
- Accession number :
- 18083042
- Full Text :
- https://doi.org/10.1016/j.cyto.2007.10.013