title: Activation of the Extracellular Signal-Regulated Kinase Signaling Is Critical for Human Umbilical Cord Mesenchymal Stem Cell Osteogenic Differentiation.
abstract: Human umbilical cord mesenchymal stem cells (hUCMSCs) are recognized as candidate progenitor cells for bone regeneration. However, the mechanism of hUCMSC osteogenesis remains unclear. In this study, we revealed that mitogen-activated protein kinases (MAPKs) signaling is involved in hUCMSC osteogenic differentiation in vitro. Particularly, the activation of c-Jun N-terminal kinases (JNK) and p38 signaling pathways maintained a consistent level in hUCMSCs through the entire 21-day osteogenic differentiation period. At the same time, the activation of extracellular signal-regulated kinases (ERK) signaling significantly increased from day 5, peaked at day 9, and declined thereafter. Moreover, gene profiling of osteogenic markers, alkaline phosphatase (ALP) activity measurement, and alizarin red staining demonstrated that the application of U0126, a specific inhibitor for ERK activation, completely prohibited hUCMSC osteogenic differentiation. However, when U0126 was removed from the culture at day 9, ERK activation and osteogenic differentiation of hUCMSCs were partially recovered. Together, these findings demonstrate that the activation of ERK signaling is essential for hUCMSC osteogenic differentiation, which points out the significance of ERK signaling pathway to regulate the osteogenic differentiation of hUCMSCs as an alternative cell source for bone tissue engineering.
authors.affiliation: Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China; Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
authors.forename: Chen-Shuang
authors.initials: CS
authors.lastname: Li
authors.affiliation: Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, CA 90095, USA.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China; Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Su
authors.affiliation: Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China; Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: University of Chicago, Chicago, IL 60637, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Ling
authors.affiliation: Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China; Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zou
authors.affiliation: Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China; Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
mesh_terms: D001861:Bone Regeneration / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D020935:MAP Kinase Signaling System / Q000235:genetics; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D010012:Osteogenesis / Q000235:genetics*; D010766:Phosphorylation; D023822:Tissue Engineering; D014470:Umbilical Cord / Q000166:cytology / Q000637:transplantation; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics
chemical_list: D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases