Involvement of SAPK/JNK in basic fibroblast growth factor-induced vascular endothelial growth factor release in osteoblasts.
We previously reported that basic fibroblast growth factor (FGF-2) activates p44/p42 mitogen-activated protein (MAP) kinase resulting in the stimulation of vascular endothelial growth factor (VEGF) release in osteoblast-like MC3T3-E1 cells and that FGF-2-activated p38 MAP kinase negatively regulates VEGF release. In the present study, we investigated the involvement of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in FGF-2-induced VEGF release in these cells. FGF-2 markedly induced the phosphorylation of SAPK/JNK. SP600125, an inhibitor of SAPK/JNK, markedly reduced the FGF-2-induced VEGF release. SP600125 suppressed the FGF-2-induced phosphorylation of SAPK/JNK without affecting the phosphorylation of p44/p42 MAP kinase or p38 MAP kinase induced by FGF-2. PD98059, an inhibitor of upstream kinase of p44/p42 MAP kinase, or SB203580, an inhibitor of p38 MAP kinase, failed to affect the FGF-2-induced phosphorylation of SAPK/JNK. A combination of SP600125 and SB203580 suppressed the FGF-2-stimulated VEGF release in an additive manner. These results strongly suggest that FGF-2 activates SAPK/JNK in osteoblasts, and that SAPK/JNK plays a part in FGF-2-induced VEGF release.
Tokuda
H
H
Department of Internal Medicine, Chubu National Hospital - National Institute for Longevity Sciences, Obu, Aichi 474-8511, Japan.
Hirade
K
K
Wang
X
X
Oiso
Y
Y
Kozawa
O
O
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002460:Cell Line; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases; D008222:Lymphokines / Q000378:metabolism*; D048670:MAP Kinase Kinase 4; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D013268:Stimulation, Chemical; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D048051:p38 Mitogen-Activated Protein Kinases
D000873:Anthracenes; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D007093:Imidazoles; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D011725:Pyridines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; C093642:SB 203580