title: Dickkopf-1 is involved in BMP9-induced osteoblast differentiation of C3H10T1/2 mesenchymal stem cells.
abstract: 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. [BMB Reports 2016; 49(3): 179-184].
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Liangbo
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Quanhe
authors.initials: Q
authors.lastname: Qiu
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Nian
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Dong
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jieliang
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hao
authors.affiliation: Department of Orthopaedic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Zhenming
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D055427:Growth Differentiation Factor 2 / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis; D015854:Up-Regulation; D060449:Wnt Signaling Pathway; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C501127:Dkk1 protein, mouse; D055427:Growth Differentiation Factor 2; D036341:Intercellular Signaling Peptides and Proteins; D048051:p38 Mitogen-Activated Protein Kinases