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-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.
Nakagawa
N
N
Research Institute of Life Science, Snow Brand Milk Products Co. Ltd. , Tochigi, 329-0512, Japan.
Yasuda
H
H
Yano
K
K
Mochizuki
S i
Si
Kobayashi
N
N
Fujimoto
H
H
Shima
N
N
Morinaga
T
T
Chikazu
D
D
Kawaguchi
H
H
Higashio
K
K
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
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