Resveratrol amplifies BMP‑4‑stimulated osteoprotegerin synthesis via p38 MAP kinase in osteoblasts

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

doi:10.3892/mmr.2015.3877

Resveratrol amplifies BMP‑4‑stimulated osteoprotegerin synthesis via p38 MAP kinase in osteoblasts

Authors:
- Gen Kuroyanagi
- Haruhiko Tokuda
- Naohiro Yamamoto
- Rie Matsushima‑Nishiwaki
- Jun Mizutani
- Osamu Kozawa
- Takanobu Otsuka
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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 501‑1194, Japan
Published online on: June 3, 2015 https://doi.org/10.3892/mmr.2015.3877
Pages: 3849-3854

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Abstract

Resveratrol is a naturally occurring polyphenol that possesses health‑related properties, and is predominantly found in grapes and berries. Bone morphogenetic protein‑4 (BMP‑4) stimulates osteocalcin synthesis via p38 mitogen‑activated protein (MAP) kinase in osteoblast‑like MC3T3‑E1 cells. The present study aimed to investigate the effects of resveratrol on BMP‑4‑induced osteoprotegerin (OPG) synthesis in MC3T3‑E1 cells. Resveratrol alone had no effect on OPG expression levels, but significantly enhanced BMP‑4‑induced OPG release. In addition, resveratrol markedly amplified the mRNA expression levels of BMP‑4‑induced OPG. SB203580 is an inhibitor of p38 MAP kinase, which was shown to suppress BMP‑4‑stimulated OPG release. BMP‑4‑induced phosphorylation of p38 MAP kinase was also enhanced by resveratrol. Furthermore, SB203580 significantly reduced the resveratrol‑induced amplification of BMP‑4‑stimulated OPG release. These results suggested that resveratrol was able to upregulate BMP‑4‑stimulated OPG synthesis via the amplification of p38 MAP kinase activity in osteoblasts.

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