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KMID : 0624620160490030179
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BMB Reports
2016 Volume.49 No. 3 p.179 ~ p.184
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Dickkopf-1 is involved in BMP9-induced osteoblast differentiation of C3H10T1/2 mesenchymal stem cells
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Lin Liangbo
Qiu Quanhe
Zhou Nian
Dong Wen
Shen Jieliang
Jiang Wei
Fang Ji
Hao Jie
Hu Zhenming
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Abstract
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Bone morphogenetic protein 9 (BMP9) is a potent inducer of osteogenic differentiation of mesenchymal stem cells. The Wnt antagonist Dickkopf-1 (Dkk1) is involved in skeletal development and bone remodeling. Here, we investigated the role of Dkk1 in BMP9-induced osteogenic differentiation of MSCs. We found that overexpression of BMP9 induced Dkk1 expression in a dose-dependent manner, which was reduced by the P38 inhibitor SB203580 but not the ERK inhibitor PD98059. Moreover, Dkk1 dramatically decreased not only BMP9-induced alkaline phosphatase (ALP) activity but also the expression of osteocalcin (OCN) and osteopontin (OPN) and matrix mineralization of C3H10T1/2 cells. Furthermore, exogenous Dkk1 expression inhibited Wnt/β-catenin signaling induced by BMP9. Our findings indicate that Dkk1 negatively regulates BMP9-induced osteogenic differentiation through inhibition of the Wnt/β-catenin pathway and it could be used to optimize the therapeutic use of BMP9 and for bone tissue engineering.
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KEYWORD
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Bone morphogenetic protein 9, Dickkopf-1, Mesenchymal stem cells, Osteoblast differentiation, Wnt/β-catenin signaling
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