Phytoestrogen Genistein induces osteoblastic differentiation of mouse bone marrow-derived mesenchymal stem cells through p38 MAPK / 中国药理学通报

ABSTRACT

Aim To investigate the role of p38 mitogen-activated protein kinases(MAPKs) in genistein-induced osteoblastic differentiation of mouse bone marrow-derived mesenchymal stem cells(BMSCs).Methods Mouse BMSCs cultured in phenol red-free ?-MEM containing 10% V/V FBS,were added ?-glycerophosphate and ascorbic acid for inducing osteoblastic differentiation,and treated with 0.01~1 ?mol?L~(-1) genistein and/or SB203580 and PD98059.The temporal sequence of osteoblastic differentiation in BMSCs cultures was assayed by measuring alkaline phosphatase activity(ALP) and calcium deposition.The MAPK phosphorylation level was detected by Western-blot.Results Genistein(0.01~1 ?mol?L~(-1)) showed a dose-dependent effect on osteoblastic differentiation as evidenced by increased alkaline phosphatase(ALP) activity and calcium deposition in mouse BMSCs cultures.Genistein(1 ?mol?L~(-1))-induced osteoblastic differentiation of BMSCs was diminished by p38 MAPK inhibitor but not the p44/42 MAPK inhibitor.The effects of Genistein were associated with rapid and sustained activation of p38 MAPK in the BMSCs cultures,which was blocked by SB203580(1 ?mol?L~(-1)).In contrast,Genistein treatment resulted in inactivation of p42/44MAPK,which was further attenuated by PD98059(25 ?mol?L~(-1)).Conclusion p38 MAPK plays an important role in genistein-induced osteoblastic differentiation of mouse BMSCs cultures.