Synovial cells from a patient with rheumatoid arthritis produce osteoclastogenesis inhibitory factor/osteoprotegerin : reciprocal regulation of the production by inflammatory cytokines and basic fibroblast growth factor

• Published in: Journal of bone and mineral metabolism Vol. 19; no. 6; pp. 365 - 372
• Main Authors: YANO, Kazuki, NAKAGAWA, Nobuaki, YASUDA, Hisataka, TSUDA, Eisuke, HIGASHIO, Kanji
• Format: Journal Article
• Language: English
• Published: Tokyo Springer 01.01.2001; Springer Nature B.V
• Subjects: Arthritis, Rheumatoid - metabolism; Biological and medical sciences; Bone Resorption; Cells, Cultured - drug effects; Culture Media, Conditioned; Cytokines; Dinoprostone - biosynthesis; Diseases of the osteoarticular system; Fibroblast Growth Factor 2 - pharmacology; Gene Expression Regulation - drug effects; Glycoproteins - genetics; Glycoproteins - metabolism; Humans; Inflammatory joint diseases; Interleukin-1 - pharmacology; Medical sciences; Nitrobenzenes - pharmacology; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Receptors, Tumor Necrosis Factor; Rheumatoid arthritis; Sulfonamides - pharmacology; Synovial Membrane - drug effects; Synovial Membrane - metabolism; Synovial Membrane - pathology; Human; Immunopathology; Cell culture; Pathogenesis; Diseases of the osteoarticular system; Cytokine; Prostaglandin E2; Resorption; Autoimmune disease; Inflammatory joint disease; Basic fibroblast growth factor; Inflammation; Osteoclast; In vitro; Chronic; Synovial membrane; Rheumatoid arthritis; Bone; Fibroblast
• ISSN: 0914-8779; 1435-5604
• DOI: 10.1007/s007740170006

To understand the involvement of osteoclastogenesis inhibitory factor (OCIF), also called osteoprotegerin (OPG), in the pathogenesis of bone destruction in rheumatoid arthritis (RA), we investigated the cytokine network involved in the production of OCIF by human fibroblast-like synovial (HFLS) cells from a patient with RA. Inflammatory cytokines, such as interleukin (IL)-1beta, IL-6 plus soluble IL-6 receptor (sIL-6R), IL-17, and tumor necrosis factor (TNF)-alpha, which are elevated in synovial fluid in RA, upregulated the production of OCIF to a level (5-20 ng/ml) sufficient to inhibit osteoclastogenesis in vitro. These inflammatory cytokines (except for IL-6 plus sIL-6R) stimulate OCIF production directly or indirectly through stimulation of prostaglandin E2 (PGE2) synthesis. In contrast to the findings with inflammatory cytokines, basic fibroblast growth factor (bFGF) inhibited the production of OCIF by the cells in a dose-dependent manner. While bFGF enhanced both the inflammatory cytokine-mediated release of PGE2 and the PGE2-mediated OCIF production, it significantly suppressed OCIF production by negating the direct stimulatory effect of the inflammatory cytokines. These findings suggest that bFGF in the synovial fluid of patients with RA may lead to severe joint destruction by suppressing the production of OCIF by HFLS cells.