(−)-epigallocatechin gallate enhances prostaglandin F2α-induced VEGF synthesis via upregulating SAPK/JNK activation in osteoblasts
✍ Scribed by Haruhiko Tokuda; Shinji Takai; Rie Matsushima-Nishiwaki; Shigeru Akamatsu; Yoshiteru Hanai; Takayuki Hosoi; Atsushi Harada; Toshiki Ohta; Osamu Kozawa
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 192 KB
- Volume
- 100
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Abstract
Catechin, one of the major flavonoids presented in plants such as tea, reportedly suppresses bone resorption. We previously reported that prostaglandin F~2α~ (PGF~2α~) stimulates the synthesis of vascular endothelial growth factor (VEGF) via p44/p42 mitogen‐activated protein (MAP) kinase in osteoblast‐like MC3T3‐E1 cells. To clarify the mechanism of catechin effect on osteoblasts, we investigated the effect of (−)‐epigallocatechin gallate (EGCG), one of the major green tea flavonoids, on the VEGF synthesis by PGF~2α~ in MC3T3‐E1 cells. The PGF~2α~‐induced VEGF synthesis was significantly enhanced by EGCG. The amplifying effect of EGCG was dose dependent between 10 and 100 µM. EGCG did not affect the PGF~2α~‐induced phosphorylation of p44/p42 MAP kinase. SB203580, a specific inhibitor of p38 MAP kinase, and SP600125, a specific inhibitor of stress‐activated protein kinase/c‐Jun N‐terminal kinase (SAPK/JNK), reduced the PGF~2α~‐induced VEGF synthesis. EGCG markedly enhanced the phosphorylation of SAPK/JNK induced by PGF~2α~ without affecting the PGF~2α~‐induced phosphorylation of p38 MAP kinase. SP600125 markedly reduced the amplification by EGCG of the SAPK/JNK phosphorylation. In addition, the PGF~2α~‐induced phosphorylation of c‐Jun was amplified by EGCG. These results strongly suggest that EGCG upregulate PGF~2α~‐stimulated VEGF synthesis resulting from amplifying activation of SAPK/JNK in osteoblasts. J. Cell. Biochem. 100: 1146–1153, 2007. © 2006 Wiley‐Liss, Inc.