期刊
PHYTOMEDICINE
卷 14, 期 12, 页码 806-814出版社
ELSEVIER GMBH, URBAN & FISCHER VERLAG
DOI: 10.1016/j.phymed.2007.04.003
关键词
resveratrol; mesenchymal stem cell; estrogen receptor; ERK1/2; p38 MAPK
资金
- NIAMS NIH HHS [R01 AR049712, R01-AR049712] Funding Source: Medline
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 [H-3]-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 RUNA2/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 17 beta-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. (c) 2007 Elsevier GmbH. All rights reserved.
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