Inhibition by minodronate of basic fibroblast growth factor-stimulated vascular endothelial growth factor synthesis
Haruhiko Tokuda1, Seiji Adachi, Rie Matsushima-Nishiwaki
1Department of Clinical Laboratory, National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Aichi 474-8511, Japan. tokuda@ncgg.go.jp.
Abstract:
In our previous study, we showed that basic fibroblast growth factor (bFGF) stimulates the synthesis of vascular endothelial growth factor (VEGF) via the activation of 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 minodronate, a newly developed bisphosphonate, on bFGF-induced VEGF synthesis in MC3T3-E1 cells. Minodronate significantly reduced the synthesis of VEGF induced by bFGF in a dose-dependent manner in a range between 3 and 100 µM. The bFGF-stimulated phosphorylation of p44/p42 MAP kinase and SAPK/JNK was reduced by minodronate. These results strongly suggest that minodronate suppresses bFGF-stimulated VEGF synthesis via the inhibition of p44/p42 MAP kinase and SAPK/JNK in osteoblasts.
Insights
Minodronate, a bisphosphonate, inhibits basic fibroblast growth factor (bFGF)-induced vascular endothelial growth factor (VEGF) synthesis in osteoblasts. It achieves this by suppressing key signaling pathways, including p44/p42 MAP kinase and SAPK/JNK.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Basic fibroblast growth factor (bFGF) stimulates vascular endothelial growth factor (VEGF) synthesis in osteoblasts.
- This stimulation involves the activation of p44/p42 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) signaling pathways.
Purpose of the Study:
- To investigate the effect of minodronate, a novel bisphosphonate, on bFGF-induced VEGF synthesis in osteoblast-like MC3T3-E1 cells.
- To elucidate the underlying molecular mechanisms of minodronate's action.
Main Methods:
- MC3T3-E1 cells were treated with bFGF and varying concentrations of minodronate.
- VEGF synthesis was measured.
- Phosphorylation levels of p44/p42 MAP kinase and SAPK/JNK were assessed using Western blotting.
Main Results:
- Minodronate significantly reduced bFGF-induced VEGF synthesis in a dose-dependent manner (3-100 µM).
- Minodronate inhibited the bFGF-stimulated phosphorylation of p44/p42 MAP kinase and SAPK/JNK.
Conclusions:
- Minodronate suppresses bFGF-stimulated VEGF synthesis in osteoblasts.
- This suppression occurs through the inhibition of p44/p42 MAP kinase and SAPK/JNK signaling pathways.
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