Basic fibroblast growth factor induces osteoclast formation by reciprocally regulating the production of osteoclast differentiation factor and osteoclastogenesis inhibitory factor in mouse osteoblastic cells

Basic fibroblast growth factor (bFGF) induced osteoclast formation in co-cu ltures of mouse spleen cells and osteoblasts. Osteoclastogenesis inhibitory factor (OCIF) and a selective cylooxygenase-2 (COX-2) inhibitor, NS-398, a bolished bFGF-induced osteoclast formation. bFGF did not affect spleen cell s, but it did affect osteoblasts, to stimulate osteoclast formation. Northe rn blot analysis revealed that bFGF up-regulated the expression of osteocla st differentiation factor (ODF) and COX-2 and down-regulated the expression of OCIF in primary osteoblastic cells. NS-398 abolished the increase of OD F mRNA, but it had no effect on the decrease of OCIF mRNA NS-398 suppressed the binding of I-125-labeled OCIF to osteoblastic cells treated with bFGF, Enzyme-linked immunosorbent assay showed that bFGF inhibited OCIF producti on by osteoblastic cells, and the inhibition was not affected by NS-398. We conclude that bFGF induces osteoclast formation by stimulating ODF product ion through COX-2-mediated prostaglandin synthesis and by suppressing OCIF production through a mechanism independent of prostaglandin synthesis. (C) 1999 Academic Press.