title: JNK MAPK is involved in BMP-2-induced odontoblastic differentiation of human dental pulp cells.
abstract: Bone morphogenetic protein-2 (BMP-2) is a multi-functional growth factor belonging to the transforming growth factor β superfamily that has a broad range of activities that affect many different cell types. BMP-2 induces odontoblastic differentiation of human dental pulp cells (DPCs), but the underlying mechanism remains unclear. In this study, we investigated the potential role of the JNK mitogen-activated protein kinases (MAPK) pathway in BMP-2-induced odontoblastic differentiation of DPCs. The levels of phosphorylated and unphosphorylated JNK MAPK were quantified by Western blot analysis following treatment with BMP-2 and the JNK inhibitor SP600125. The role of JNK MAPK in the BMP-2-induced odontoblastic differentiation of DPCs was determined by measuring alkaline phosphatase (ALP) activity and by examining the expression of odontoblastic markers using quantitative real-time polymerase chain reaction analysis. The effect of JNK MAPK silencing on odontoblastic differentiation was also investigated. BMP-2 upregulated the phosphorylation of JNK in DPCs in a dose- and time-dependent manner. Early markers of odontoblastic differentiation, including ALP activity, osteopontin and dentin matrix protein-1, were not inhibited by the JNK inhibitor. However, the JNK inhibitor, SP600125, significantly inhibited late-stage differentiation of odontoblasts, including the gene expression of osteocalcin, dentin sialophosphoprotein and bone sialoprotein, and also reduced the formation of mineralized nodules in BMP-2-treated DPCs. Consistent with this observation, silencing of JNK MAPK also decreased late-stage odontoblastic differentiation. Taken together, these findings suggest that JNK activity is required for late-stage odontoblastic differentiation induced by BMP-2.
authors.affiliation: Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University , Guangzhou , China .
authors.forename: Wei
authors.initials: W
authors.lastname: Qin
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Liu
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Shuheng
authors.initials: S
authors.lastname: Huang
authors.forename: Xianling
authors.initials: X
authors.lastname: Gao
authors.forename: Zhi
authors.initials: Z
authors.lastname: Song
authors.forename: Runfu
authors.initials: R
authors.lastname: Wang
authors.forename: Lingling
authors.initials: L
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: Guo
authors.forename: Zhengmei
authors.initials: Z
authors.lastname: Lin
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D003782:Dental Pulp / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009804:Odontoblasts / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D016212:Transforming Growth Factor beta; D048031:JNK Mitogen-Activated Protein Kinases