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.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Prostaglandins, Leukotrienes and Essential Fatty AcidsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Reaching a genetic and molecular understanding of skeletal development.Dev. Cell. 2002; 2: 389-406
- Targeted and nontargeted bone remodeling: relationship to basic multice.Bone. 2002; 30: 5-7
- Osteoclast biology and bone resorption.in: Rosen C.J. Primer on the Metabolic Bone Diseases of Minerel Metabolism. 8th ed. John Wiley & Sons, Inc., Hoboken, NJ2013
- Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.Cell. 1997; 89: 309-319
- Transgenic mice overexpressing soluble osteoclast differentiation factor (sODF) exhibit severe osteoporosis.J. Bone Miner. Metab. 2002; 20: 337-344
- The roles of prostanoids, leukotrienes, and platelet-activating factor in bone metabolism and disease.Prog. Lipid Res. 2008; 47: 107-126
- Prostaglandin D2 metabolite stimulates collagen synthesis by human osteoblasts during calcification.Prostaglandins. 1991; 41: 303-313
- Production of prostaglandin D2 by human osteoblasts and modulation of osteoprotegerin, RANKL, and cellular migration by DP and CRTH2 receptors.J. Bone Miner. Res. 2005; 20: 672-681
- Prostaglandin D2 induces interleukin-6 synthesis via Ca2+ mobilization in osteoblasts: regulation by protein kinase C.Prostaglandins Leukot. Essent. Fat. Acids. 1999; 61: 189-194
- Function of Rho-kinase in prostaglandin D2-induced interleukin-6 synthesis in osteoblasts.Prostaglandins Leukot. Essent. Fat. Acids. 2008; 79: 41-46
- Mechanism of prostaglandin D2-stimulated heat shock protein 27 induction in osteoblasts.Cell. Signal. 2001; 13: 535-541
- Rho-kinase regulates prostaglandin D2-stimulated heat shock protein 27 induction in osteoblasts.Exp. Ther. Med. 2010; 1: 579-583
- Why drinking green tea could prevent cancer.Nature. 1997; 387: 561
- Advances in flavonoid research since 1992.Phytochemistry. 2000; 55: 481-504
- Resveratrol improves health and survival of mice on a high-calorie diet.Nature. 2006; 444: 37-42
- In vino veritas: a tale of two sirt1s?.Cell. 2006; 127: 1091-1093
- Wine, alcohol, platelets, and the French paradox for coronary heart disease.Lancet. 1992; 339: 1523-1526
- Preference for wine is associated with lower hip fracture incidence in post-menopausal women.BMC Women’s Health. 2013; 13: 36
- in vivo differentiation and calcification in a new clonal osteogenic cell line derived from newborn mouse calvaria.J. Cell Biol. 1983; 96: 191-198
- Cross-talk regulation between cyclic AMP production and phosphoinositide hydrolysis induced by prostaglandin E2 in osteoblast-like cells.Exp. Cell. Res. 1992; 198: 130-134
- Cleavage of structural proteins during the assembly of the head of bacteriophage T4.Nature. 1970; 227: 680-685
- Modulation of the stress-induced synthesis of hsp27 and αB-crystallin by cyclic AMP in C6 glioma cells.J. Neurochem. 1996; 66: 946-950
- Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes.Nature. 2007; 450: 712-716
- Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation.Physiol. Rev. 2001; 81: 807-869
- PD98059 is a specific inhibitor of the activation of mitogen-activated protein kinase in vitro and in vivo.J. Biol. Chem. 1995; 270: 27489-27494
- SB203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1.FEBS Lett. 1995; 364: 229-233
- SP600125, an anthrapyrazolone inhibitor of Jun N-terminal Kinase.Proc. Natl. Acad. Sci. U.S.A. 2001; 98: 13681-13686
- Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells.Trends Pharmacol. Sci. 2001; 22: 32-39
- Myosin phosphatase: structure, regulation and function.Mol. Cell. Biochem. 2004; 259: 197-209
- Prostaglandin D2 stimulates calcification of human osteoblastic cells.Biochem. Biophys. Res. Commun. 1989; 159: 1206-1212
- High absorption but very low bioavailability of oral resveratrol in humans.Drug Metab. Dispos. 2004; 32: 1377-1382
- CSF levels of prostaglandins, especially the level of prostaglandin D2, are correlated with increasing propensity towards sleep in rats.Brain Res. 1997; 751: 81-89
Article info
Publication history
Published online: April 24, 2014
Accepted:
April 17,
2014
Received in revised form:
April 7,
2014
Received:
October 30,
2013
Identification
Copyright
© 2014 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
