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

Abstract

To investigate the effect of the synovial fluid from knee joints of rheumatoid arthritis (RA) patients with different severities of joint destruction on osteoclastogenesis and bone resorption. Synovial fluid was harvested from the knee joints of 59 RA patients and 37 ostcoarthritis (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 severe RA (n = 29). Cytokine concentrations in synovial fluid were measured by ELISA. Osteoclastogenesis was measured by tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell (MNC) formation in a co-culture of mouse osteoblastic cells and bone marrow cells, and bone resorption by 45Ca release from pre-labelled cultured neonatal mouse calvariae. The synovial fluid of severe RA patients significantly stimulated TRAP-positive MNC formation and 45Ca release compared to those of mild RA and OA patients. Among the bone-resorptive cytokines fibroblast growth factor-2 (FGF-2), tumour necrosis factor alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), IL-6 and soluble IL-6 receptor (sIL-6R), only FGF-2 concentration in the synovial fluid was positively correlated to Larsen's grade, and severe RA patients showed significantly higher FGF-2 concentrations than mild RA patients. Osteoclastogenesis in a co-culture system which was stimulated 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. The increase in endogenous FGF-2 levels in the synovial fluid of RA patients may play a role in the joint destruction by inducing osteoclastogenesis.