Research Article

Syringetin, a flavonoid derivative in grape and wine, induces human osteoblast differentiation through bone morphogenetic protein-2/extracellular signal-regulated kinase 1/2 pathway

  1. Ya-Ling Hsu1,
  2. Hsin-Lin Liang2,3,
  3. Chih-Hsing Hung1,4,
  4. Po-Lin Kuo5,6,*

Article first published online: 25 SEP 2009

DOI: 10.1002/mnfr.200800483

Issue

Molecular Nutrition & Food Research

Molecular Nutrition & Food Research

Volume 53, Issue 11, pages 1452–1461, November 2009

Additional Information

How to Cite

Hsu, Y.-L., Liang, H.-L., Hung, C.-H. and Kuo, P.-L. (2009), Syringetin, a flavonoid derivative in grape and wine, induces human osteoblast differentiation through bone morphogenetic protein-2/extracellular signal-regulated kinase 1/2 pathway. Mol. Nutr. Food Res., 53: 1452–1461. doi: 10.1002/mnfr.200800483

Author Information

  1. 1

    Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

  2. 2

    Department of Pharmacology, Kaohsiung Municipal United Hospital, Kaohsiung, Taiwan

  3. 3

    School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan

  4. 4

    Department of Pediatrics, Faculty of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

  5. 5

    Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

  6. 6

    Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

*Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan Fax: +886-7-321-0701

Publication History

  1. Issue published online: 6 NOV 2009
  2. Article first published online: 25 SEP 2009
  3. Manuscript Accepted: 22 MAR 2009
  4. Manuscript Revised: 12 JAN 2009
  5. Manuscript Received: 21 OCT 2008

Funded by

  • National Science Council of Taiwan. Grant Number: NSC 96-2320-B-041-004-MY2
  • Kaohsiung Medical University Research Foundation. Grant Number: KMU-Q098031

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Keywords:

  • Bone morphogenetic protein-2;
  • Differentiation;
  • Extracellular signal-regulated kinase1/2;
  • Osteoblasts;
  • Syringetin

Abstract

Syringetin (3,5,7,4′-tetrahydroxy-3′,5′dimethoxyflavone), a flavonoid derivative, is present in grape and wine. By means of alkaline phosphatase (ALP) activity, osteocalcin, and type I collagen ELISA, we have shown that syringetin exhibits a significant induction of differentiation in MC3T3-E1 mouse calvaria osteoblasts and human fetal osteoblastic 1.19 cell line human osteoblasts. ALP and osteocalcin are phenotypic markers for early-stage differentiated osteoblasts and terminally differentiated osteoblasts, respectively. Our results indicate that syringetin stimulates osteoblast differentiation at various stages, from maturation to terminally differentiated osteoblasts. Induction of differentiation by syringetin is associated with increased bone morphogenetic protein-2 (BMP-2) production. The BMP-2 antagonist noggin blocked syringetin-mediated ALP activity and osteocalcin secretion enhancement, indicating that BMP-2 production is required in syringetin-mediated osteoblast maturation and differentiation. Induction of differentiation by syringetin is associated with increased activation of SMAD1/5/8 and extracellular signal-regulated kinase 1/2 (ERK1/2). Cotreatment of ERK1/2 inhibitor 2′-amino-3′-methoxyflavone inhibited syringetin-mediated ALP upregulation and osteocalcin production. In conclusion, syringetin increased BMP-2 synthesis, and subsequently activated SMAD1/5/8 and ERK1/2, and this effect may contribute to its action on the induction of osteoblast maturation and differentiation, followed by an increase of bone mass.

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