Resveratrol enhances proliferation and osteoblastic differentiation in human mesenchymal stem cells via ER-dependent ERK1/2 activation |
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Authors: | Z Dai Y Li LD Quarles T Song W Pan H Zhou Z Xiao |
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Institution: | aInstitute of Clinical Pharmacology, Central South University, Changsha 410078, China bThe Kidney Institute, University of Kansas Medical Center, MS 3018, 3901 Rainbow Boulevard, 6018 Wahl Hall East, Kansas City, KS 66160, USA cInstitute of Reproduction and Stem Cell Engineering, Central South University, Changsha 410078, China |
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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. |
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Keywords: | Resveratrol Mesenchymal stem cell Estrogen receptor ERK1/2 P38 MAPK |
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