title: Enhancement of basic fibroblast growth factor-stimulated VEGF synthesis by Wnt3a in osteoblasts.
abstract: It is currently recognized that the Wnt signaling pathway regulates bone mass. We have previously reported that the basic fibroblast growth factor (FGF-2) stimulates the synthesis of the vascular endothelial growth factor (VEGF) at least in part via the p44/p42 mitogen-activated protein (MAP) kinase and the stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect of Wnt3a on FGF-2-stimulated VEGF synthesis in MC3T3-E1 cells. Wnt3a significantly augmented the FGF-2-stimulated VEGF release in a dose-dependent manner in the range between 1 and 30 ng/ml. Lithium chloride and SB216763, inhibitors of glycogen synthase kinase 3β (GSK3β), enhanced the FGF-2-stimulated VEGF release. Wnt3a did not affect the phosphorylation of the p44/p42 MAP kinase, SAPK/JNK, Akt, p38 MAP kinase or the p70 S6 kinase induced by FGF-2. Wnt3a and SB216763 increased the levels of VEGF mRNA expression induced by FGF-2. These results strongly suggest that Wnt3a enhances VEGF synthesis stimulated by FGF-2 via activation of the canonical Wnt/β-catenin pathway in osteoblasts.
authors.affiliation: Department of Clinical Laboratory, National Center for Geriatrics and Gerontology, Obu, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Tokuda
authors.forename: Seiji
authors.initials: S
authors.lastname: Adachi
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Kato
authors.forename: Hideo
authors.initials: H
authors.lastname: Natsume
authors.forename: Takanobu
authors.initials: T
authors.lastname: Otsuka
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics; D051153:Wnt Proteins / Q000378:metabolism*; D060508:Wnt3 Protein; D060509:Wnt3A Protein
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D016222:Fibroblast Growth Factor 2; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases