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- Title
Potentiation by platelet-derived growth factor-BB of FGF-2-stimulated VEGF release in osteoblasts.
- Authors
Tokuda, Haruhiko; Takai, Shinji; Hanai, Yoshiteru; Harada, Atsushi; Matsushima-Nishiwaki, Rie; Kato, Hisaaki; Ogura, Shinji; Kozawa, Osamu
- Abstract
We previously reported that basic fibroblast growth factor (FGF-2) stimulates the release of vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect of platelet-derived growth factor-BB (PDGF-BB) on FGF-2-induced VEGF release in MC3T3-E1 cells. PDGF-BB significantly enhanced the FGF-2-stimulated VEGF release. The amplifying effect of PDGF-BB was dose dependent in the range between 0.1 and 30 ng/ml. AG1295, a selective inhibitor of PDGF receptor kinase, which reduced the autophosphorylation of PDGF receptor-(R), suppressed the enhancement by PDGF-BB without affecting the FGF-2 effect. PDGF-BB failed to strengthen the FGF-2-induced phosphorylation of p44/p42 MAP kinase or SAPK/JNK. The amplification by PDGF-BB of FGF-2-stimulated VEGF release was reduced by PD98059, a specific inhibitor of MEK, or SP600125, a specific inhibitor of SAPK/JNK. These results strongly suggest that PDGF-BB potentiates FGF-2-stimulated VEGF release at a point downstream from p44/p42 MAP kinase and SAPK/JNK in osteoblasts.
- Subjects
ANIMAL experimentation; ANIMAL populations; BIOLOGICAL models; CELL lines; CELL receptors; COMPARATIVE studies; DRUG synergism; DOSE-effect relationship in pharmacology; FLAVONOIDS; GROWTH factors; HYDROCARBONS; RESEARCH methodology; MEDICAL cooperation; MICE; PHOSPHORYLATION; PLATELET-derived growth factor; PROTEINS; RESEARCH; TRANSFERASES; EVALUATION research; VASCULAR endothelial growth factors; OSTEOBLASTS
- Publication
Journal of Bone & Mineral Metabolism, 2008, Vol 26, Issue 4, p335
- ISSN
0914-8779
- Publication type
journal article
- DOI
10.1007/s00774-007-0829-x