Resveratrol inhibits BMP-4-stimulated VEGF synthesis in osteoblasts: Suppression of S6 kinase

Kondo,Akira; Otsuka,Takanobu; Kuroyanagi,Gen; Yamamoto,Naohiro; Matsushima-Nishiwaki,Rie; Mizutani,Jun; Kozawa,Osamu; Tokuda,Haruhiko

doi:10.3892/ijmm.2014.1626

Resveratrol inhibits BMP-4-stimulated VEGF synthesis in osteoblasts: Suppression of S6 kinase

Authors:
- Akira Kondo
- Takanobu Otsuka
- Gen Kuroyanagi
- Naohiro Yamamoto
- Rie Matsushima-Nishiwaki
- Jun Mizutani
- Osamu Kozawa
- Haruhiko Tokuda
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Affiliations: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan, Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan
Published online on: January 17, 2014 https://doi.org/10.3892/ijmm.2014.1626
Pages: 1013-1018

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Abstract

Resveratrol is well known as a natural polyphenol abundantly found in red wine. We previously reported that bone morphogenetic protein-4 (BMP-4) stimulates vascular endothelial growth factor (VEGF) synthesis via p70 S6 kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect of resveratrol on the BMP-4-stimulated VEGF synthesis in MC3T3-E1 cells. Resveratrol significantly suppressed BMP-4-stimulated release and expression levels of VEGF mRNA. SRT1720, an activator of SIRT1 with potencies greater than resveratrol, also reduced VEGF release and the mRNA levels. Both resveratrol and SRT1720 markedly attenuated the BMP-4-induced phosphorylation of p70 S6 kinase without affecting the BMP-4-induced phosphorylation of Smad1/5/8. These findings strongly suggest that resveratrol attenuates BMP-4-stimulated VEGF synthesis through suppression of the activation of p70 S6 kinase in osteoblasts, and that the inhibitory effect is mediated at least in part by SIRT1 activation.

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