title: Basic fibroblast growth factor induces osteoclast formation by reciprocally regulating the production of osteoclast differentiation factor and osteoclastogenesis inhibitory factor in mouse osteoblastic cells.
abstract: 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 (125)I-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.
authors.affiliation: Research Institute of Life Science, Snow Brand Milk Products Co. Ltd. , Tochigi, 329-0512, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Nakagawa
authors.forename: H
authors.initials: H
authors.lastname: Yasuda
authors.forename: K
authors.initials: K
authors.lastname: Yano
authors.forename: S i
authors.initials: Si
authors.lastname: Mochizuki
authors.forename: N
authors.initials: N
authors.lastname: Kobayashi
authors.forename: H
authors.initials: H
authors.lastname: Fujimoto
authors.forename: N
authors.initials: N
authors.lastname: Shima
authors.forename: T
authors.initials: T
authors.lastname: Morinaga
authors.forename: D
authors.initials: D
authors.lastname: Chikazu
authors.forename: H
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: K
authors.initials: K
authors.lastname: Higashio
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology; D018920:Coculture Techniques; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000187:drug effects / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology; D008565:Membrane Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D009578:Nitrobenzenes / Q000494:pharmacology; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D053244:Osteoprotegerin; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013449:Sulfonamides / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D002352:Carrier Proteins; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D006023:Glycoproteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009578:Nitrobenzenes; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D013449:Sulfonamides; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D016222:Fibroblast Growth Factor 2; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases