JNK MAPK is involved in BMP-2-induced odontoblastic differentiation of human dental pulp cells

• Published in: Connective tissue research 2014-06, Vol.55 (3), p.217-224
• Main Authors: Qin, Wei, Liu, Pengcheng, Zhang, Rong, Huang, Shuheng, Gao, Xianling, Song, Zhi, Wang, Runfu, Chen, Lingling, Guo, Bing, Lin, Zhengmei
• Format: Article
• Language: English
• Subjects: Bone morphogenetic protein; Bone Morphogenetic Protein 2 - metabolism; Cell Differentiation - physiology; Dental Pulp - cytology; Dental Pulp - metabolism; dental pulp cells; differentiation; Humans; JNK; JNK Mitogen-Activated Protein Kinases - metabolism; odontoblast; Odontoblasts - cytology; Odontoblasts - metabolism; Signal Transduction - physiology; Transforming Growth Factor beta - metabolism
• ISSN: 0300-8207; 1607-8438
• DOI: 10.3109/03008207.2014.882331

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.