Basic Fibroblast Growth Factor Induces Osteoclast Formation by Reciprocally Regulating the Production of Osteoclast Differentiation Factor and Osteoclastogenesis Inhibitory Factor in Mouse Osteoblastic Cells

• Published in: Biochemical and biophysical research communications 1999-11, Vol.265 (1), p.158-163
• Main Authors: Nakagawa, Nobuaki, Yasuda, Hisataka, Yano, Kazuki, Mochizuki, Shin-ichi, Kobayashi, Naoki, Fujimoto, Hitoshi, Shima, Nobuyuki, Morinaga, Tomonori, Chikazu, Daichi, Kawaguchi, Hiroshi, Higashio, Kanji
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Carrier Proteins - genetics; Carrier Proteins - pharmacology; Carrier Proteins - physiology; Coculture Techniques; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Fibroblast Growth Factor 2 - drug effects; Fibroblast Growth Factor 2 - pharmacology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Glycoproteins - genetics; Glycoproteins - physiology; Humans; Isoenzymes - metabolism; Membrane Glycoproteins - genetics; Membrane Glycoproteins - pharmacology; Membrane Glycoproteins - physiology; Membrane Proteins; Mice; Mice, Inbred Strains; Nitrobenzenes - pharmacology; osteoclast differentiation factor; Osteoclastogenesis inhibitory factor; Osteoclasts - cytology; Osteoclasts - drug effects; Osteoclasts - physiology; Osteoprotegerin; Prostaglandin-Endoperoxide Synthases - metabolism; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Recombinant Proteins - pharmacology; Spleen - cytology; Sulfonamides - pharmacology; Transcription, Genetic - drug effects
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1999.1601

Basic fibroblast growth factor (bFGF) induced osteoclast formation in co-cultures of mouse spleen cells and osteoblasts. Osteoclastogenesis inhibitory factor (OCIF) and a selective cyclooxygenase-2 (COX-2) inhibitor, NS-398, abolished bFGF-induced osteoclast formation. bFGF did not affect spleen cells, but it did affect osteoblasts, to stimulate osteoclast formation. Northern blot analysis revealed that bFGF up-regulated the expression of osteoclast differentiation factor (ODF) and COX-2 and down-regulated the expression of OCIF in primary osteoblastic cells. NS-398 abolished the increase of ODF mRNA, but it had no effect on the decrease of OCIF mRNA. NS-398 suppressed the binding of 125I-labeled OCIF to osteoblastic cells treated with bFGF. Enzyme-linked immunosorbent assay showed that bFGF inhibited OCIF production by osteoblastic cells, and the inhibition was not affected by NS-398. We conclude that bFGF induces osteoclast formation by stimulating ODF production through COX-2-mediated prostaglandin synthesis and by suppressing OCIF production through a mechanism independent of prostaglandin synthesis.