Potentiation by platelet-derived growth factor-BB of FGF-2-stimulated VEGF release in osteoblasts

被引:13
作者
Tokuda, Haruhiko [1 ,2 ]
Takai, Shinji [2 ]
Hanai, Yoshiteru [1 ,2 ]
Harada, Atsushi [3 ]
Matsushima-Nishiwaki, Rie [2 ]
Kato, Hisaaki [2 ,4 ]
Ogura, Shinji [4 ]
Kozawa, Osamu [2 ]
机构
[1] Natl Hosp Geriatr Med, Dept Clin Lab, Natl Ctr Geriatr & Gerontol, Aichi 4748511, Japan
[2] Gifu Univ, Dept Pharmacol, Grad Sch Med, Gifu, Japan
[3] Natl Hosp Geriatr Med, Dept Funct Restorat, Natl Ctr Geriatr & Gerontol, Aichi, Japan
[4] Gifu Univ, Dept Emergency & Disaster Med, Grad Sch Med, Gifu, Japan
关键词
FGF; PDGF; MAP kinase; VEGF; osteoblast;
D O I
10.1007/s00774-007-0829-x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We previously reported that basic fibroblast growth factor (FGF-2) stimulates the release of vascular endothelial growth factor (VEGF) via p44/p42 mitogenactivated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblastlike 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.
引用
收藏
页码:335 / 341
页数:7
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