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  • Suppression by resveratrol of prostaglandin D2-stimulated osteoprotegerin synthesis in osteoblasts.

Suppression by resveratrol of prostaglandin D2-stimulated osteoprotegerin synthesis in osteoblasts.

Prostaglandins, leukotrienes, and essential fatty acids (2014-05-13)
Gen Kuroyanagi, Jun Mizutani, Akira Kondo, Naohiro Yamamoto, Rie Matsushima-Nishiwaki, Takanobu Otsuka, Osamu Kozawa, Haruhiko Tokuda
ABSTRACT

Resveratrol, a natural polyphenol with health-related properties mainly existing in grape skins and red wine, possesses beneficial effects on human being. We have previously reported that prostaglandin D2 (PGD2) stimulates heat shock protein 27 (HSP27) induction via activation of p44/p42 mitogen-activated protein (MAP) kinase, p38 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 mechanism behind the effect of PGD2 on osteoprotegerin (OPG) synthesis and the effect of resveratrol on the OPG synthesis in MC3T3-E1 cells. PGD2 significantly stimulated both the OPG release and the expression levels of OPG mRNA. Resveratrol and SRT1720, an activator of SIRT1, markedly suppressed the PGD2-induced OPG release and the mRNA levels of OPG. PD98059, a specific MEK inhibitor, SB203580, a specific p38 MAP kinase inhibitor, and SP600125, a specific SAPK/JNK inhibitor suppressed the PGD2-stimulated OPG release. PGD2-induced phosphorylation of p38 MAP kinase and SAPK/JNK was attenuated by resveratrol or SRT1720. However, resveratrol or SRT1720 failed to affect the phosphorylation of myosin phosphatase-targeting subunit-1 (MYPT-1), a downstream substrate of Rho-kinase and p44/p42 MAP kinase. These results strongly suggest that resveratrol suppresses PGD2-stimulated OPG synthesis through inhibiting p38 MAP kinase and SAPK/JNK in osteoblasts, and that the suppressive effect is exerted at the point downstream of Rho-kinase but upstream of p38 MAP kinase or SAPK/JNK.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Mouse TRANCE ELISA Kit, for serum, plasma and cell culture supernatant
Sigma-Aldrich
Human Osteoprotegerin / TNFRSF11b ELISA Kit, for serum, plasma, cell culture supernatant and urine
Sigma-Aldrich
Prostaglandin D2, ≥95%, synthetic
Supelco
Resveratrol, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Supelco
Resveratrol, analytical standard
Sigma-Aldrich
Resveratrol, ≥99% (HPLC)
Resveratrol, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Mouse Osteoprotegerin ELISA Kit, for serum, plasma, cell culture supernatant