(−)‐epigallocatechin gallate enhances prostaglandin F_2α‐induced VEGF synthesis via upregulating SAPK/JNK activation in osteoblasts

Abstract

Catechin, one of the major flavonoids presented in plants such as tea, reportedly suppresses bone resorption. We previously reported that prostaglandin F(2alpha) (PGF(2alpha)) 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(2alpha) in MC3T3-E1 cells. The PGF(2alpha)-induced VEGF synthesis was significantly enhanced by EGCG. The amplifying effect of EGCG was dose dependent between 10 and 100 microM. EGCG did not affect the PGF(2alpha)-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(2alpha)-induced VEGF synthesis. EGCG markedly enhanced the phosphorylation of SAPK/JNK induced by PGF(2alpha) without affecting the PGF(2alpha)-induced phosphorylation of p38 MAP kinase. SP600125 markedly reduced the amplification by EGCG of the SAPK/JNK phosphorylation. In addition, the PGF(2alpha)-induced phosphorylation of c-Jun was amplified by EGCG. These results strongly suggest that EGCG upregulate PGF(2alpha)-stimulated VEGF synthesis resulting from amplifying activation of SAPK/JNK in osteoblasts.

When nutrition interacts with osteoblast function: molecular mechanisms of polyphenols

“…It has been shown that 60 min of pre-treatment with 10 mM-EGCG amplified PGF 2a -induced phosphorylation of c-jun which is a part of the AP-1 complex and well known as a downstream effector of SAPK/JNK (82) .…”

Selective removal of caffeine from tea extracts using macroporous crosslinked polyvinyl alcohol adsorbents

“…1A. As well as being a valuable source of antioxidants in the food industry, interest in TPh has increased to medicine, health products, cosmetics, fine chemicals and other applications owing to its pharmacological effects of scavenging free radicals [3,4]. Another active component in tea is a kind of alkaloid, namely caffeine (CAF), which is present in green tea at levels of around 2-5%, as shown in Fig.…”

(−)-Epigallocatechin gallate attenuates the induction of HSP27 stimulated by sphingosine 1-phosphate via suppression of phosphatidylinositol 3-kinase/Akt pathway in osteoblasts

“…As for osteoblasts, it was shown that catechin stimulates alkaline phosphatase activity, a mature osteoblast phenotype and reduces the production of bone-resorptive cytokines, such as tumor necrosis factor-· (TNF-·) and interleukin-6 (IL-6) in osteoblast-like MC3T3-E1 cells (21). On the other hand, we reported that (-)-epigallocatechin gallate (EGCG) enhances vascular endothelial growth factor (VEGF) synthesis stimulated by prostaglandin F2 · via upregulating stressactivated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) activation in MC3T3-E1 cells (22). In addition, we recently reported that EGCG inhibits prostaglandin D2-stimulated HSP27 induction via suppression of the p44/p42 MAP kinase pathway in these cells (23).…”