Involvement of fibroblast growth factor-2 in joint destruction of rheumatoid arthritis patients

Objective. To investigate the effect of the synovial fluid ft om knee joint s of rheumatoid arthritis (RA) patients with different severities of joint destruction on osteoclastogenesis and bone resorption. Methods. Synovial fluid was harvested From the knee joints of 59 RA patient s and 37 osteoarthritis (OA) patients. RA patients with Larsen's knee grade 1-3 were classified as mild RA (n = 30) and those with grade 4 or 5 as sev ere RE (n = 29). Cytokine concentrations in synovial fluid were measured by ELISA. Osteoclastogenesis was measured by tartrate-resistant acid phosphat ase (TRAP)-positive multinucleated cell (MNC) formation in a co-culture of mouse osteoblastic cells and bone marrow cells, and bone resorption by Ca-4 5 release from pre-labelled cultured neonatal mouse calvariae. Results. The synovial fluid of severe RA patients significantly stimulated TRAP-positive MNC formation and Ca-45 release compared to those of mild RA and OA patients. Among the bone-resorptive cytokines fibroblast growth fact or-2 (FGF-2), tumour necrosis Factor alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) IL-6 and soluble IL-6 receptor (sIL-6R), only FGF-7 concentra tion in the synovial fluid was positively correlated to Larsen's grade, and severe RA patients showed significantly higher FGF-2 concentrations han mi ld RA patients. Osteoclastogenesis in a co-culture system which was stimula ted by the synovial fluid of severe RA patients was significantly inhibited by a neutralizing antibody against FGF-2 and this inhibition was stronger than antibodies against other cytokines. Conclusion. The increase in endogenous FGF-2 levels in the synovial fluid o f RA patients may play a role in the joint destruction by inducing osteocla stogenesis.