Resveratrol enhances proliferation and osteoblastic differentiation in human mesenchymal stem cells via ER-dependent ERK1/2 activation

Z. Dai, Y. Li, L. D. Quarles, T. Song, W. Pan, H. Zhou, Z. Xiao

Research output: Contribution to journalArticle

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Abstract

In the present study, we investigated the in vitro effect of resveratrol (RSVL), a polyphenolic phytoestrogen, on cell proliferation and osteoblastic maturation in human bone marrow-derived mesenchymal stem cell (HBMSC) cultures. RSVL (10-8-10-5 M) increased cell growth dose-dependently, as measured by [3H]-thymidine incorporation, and stimulated osteoblastic maturation as assessed by alkaline phosphatase (ALP) activity, calcium deposition into the extracellular matrix, and the expression of osteoblastic markers such as RUNX2/CBFA1, Osterix and Osteocalcin in HBMSCs cell cultures. Further studies found that RSVL (10-6 M) resulted in a rapid activation of both extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) signaling in HBMSCs cultures. The effects of RSVL were mimicked by 17β-estrodial (10-8 M) and were abolished by estrogen receptor (ER) antagonist ICI182780. An ERK1/2 pathway inhibitor, PD98059, significantly attenuated RSVL-induced ERK1/2 phosphorylation, consistent with the reduction of cell proliferation and osteoblastic differentiation as well as expression of osteoblastic markers. In contrast, SB203580, a p38 MAPK pathway blocker, blocked RSVL-induced p38 phosphorylation, but resulted in an increase of cell proliferation and a more osteoblastic maturation. These data suggest that RSVL stimulates HBMSCs proliferation and osteoblastic differentiation through an ER-dependent mechanism and coupling to ERK1/2 activation.

Original languageEnglish (US)
Pages (from-to)806-814
Number of pages9
JournalPhytomedicine
Volume14
Issue number12
DOIs
StatePublished - Dec 4 2007

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Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Mesenchymal Stromal Cells
Estrogen Receptors
Cell Proliferation
p38 Mitogen-Activated Protein Kinases
Cell Culture Techniques
Phosphorylation
Phytoestrogens
Osteocalcin
resveratrol
Thymidine
Extracellular Matrix
Alkaline Phosphatase
Bone Marrow
Calcium
Growth

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine

Cite this

Resveratrol enhances proliferation and osteoblastic differentiation in human mesenchymal stem cells via ER-dependent ERK1/2 activation. / Dai, Z.; Li, Y.; Quarles, L. D.; Song, T.; Pan, W.; Zhou, H.; Xiao, Z.

In: Phytomedicine, Vol. 14, No. 12, 04.12.2007, p. 806-814.

Research output: Contribution to journalArticle

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