title: Fibroblast growth factor 2 inhibits bone morphogenetic protein 9-induced osteogenic differentiation of mesenchymal stem cells by repressing Smads signaling and subsequently reducing Smads dependent up-regulation of ALK1 and ALK2.
abstract: Understanding the interactions between growth factors and bone morphogenic proteins (BMPs) signaling remains a crucial issue to optimize the use of mesenchymal stem cells (MSCs) and BMPs in bone tissue engineering. BMP9 is highly capable of promoting osteogenic differentiation of MSCs. Fibroblast growth factor 2 (FGF2) is abundantly secreted during the healing process of fractures or in surgery bone sites. Herein, we explore the detail effect of FGF2 on BMP9-induced osteogenic differentiation of MSCs. It was found that FGF2 inhibited BMP9-induced osteogenic differentiation by blocking BMP9-induced Smads signaling and subsequently reducing Smads dependent up-regulation of ALK1 and ALK2 in MSCs. This effect was rescued by exogenous expression of ALK1 and ALK2, which are proved to be receptors for BMP9. Our results discovered a clue to explain the mechanism involved in the inhibitory effect of FGF2 on BMP9-induced osteogenic differentiation of MSCs. This crosstalk between FGF2 and BMP9 should be emphasized in the future use of BMP9 in therapeutic purpose of fracture repair.
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 40016, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Song
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Qian
authors.initials: Q
authors.lastname: Dong
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.forename: Xinglian
authors.initials: X
authors.lastname: Duan
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Liang
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiao
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Juanwen
authors.initials: J
authors.lastname: He
authors.forename: Ming
authors.initials: M
authors.lastname: Tang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Jinyong
authors.initials: J
authors.lastname: Luo
mesh_terms: D030201:Activin Receptors, Type I / Q000378:metabolism*; D030301:Activin Receptors, Type II; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D055427:Growth Differentiation Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D055427:Growth Differentiation Factor 2; C493716:Runx2 protein, mouse; D051785:Smad Proteins; D016222:Fibroblast Growth Factor 2; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II; C498943:Acvr1 protein, mouse; C498931:Acvrl1 protein, mouse; D000469:Alkaline Phosphatase
keywords: Bone morphogenic proteins 9; Fibroblast growth factor 2; Mesenchymal stem cells; Osteogenic differentiation; Smads