title: WNT6 promotes the migration and differentiation of human dental pulp cells partly through c-Jun N-terminal kinase signaling pathway.
abstract: BACKGROUND
  During the dental pulp repair process, human dental pulp cells (HDPCs) migrate to injury sites where they may differentiate into odontoblastlike cells. WNT6 plays a role in dental development and can activate a noncanonical pathway including the c-Jun N-terminal kinase (JNK) pathway. The mechanism of WNT6 in dental pulp repair is still unknown. The purpose of this study was to explore the potential role of the WNT6/JNK signaling pathway in the promotion of cell migration and the differentiation of HDPCs.
  
  
  METHODS
  The third passage of HDPCs were cultured in vitro and treated with WNT6 conditioned medium with or without the pretreatment of JNK inhibitor SP600125. The activation of JNK was detected by Western blot, the expression of c-Jun was quantified by reverse-transcription polymerase chain reaction, the migration of HDPCs was determined by wound healing and transwell migration assays, and the differentiation of HDPCs was investigated using alkaline phosphatase staining and alizarin red staining. The expression of odontogenesis-related genes such as Runt-related transcription factor 2, dentin sialophosphoprotein, and dentin matrix protein 1 was quantified.
  
  
  RESULTS
  WNT6 activates the JNK pathway in HDPCs and enhances cell migration, mineralization nodule formation, and alkaline phosphatase activation. WNT6 also increases the expression of Runt-related transcription factor 2, dentin sialophosphoprotein, and dentin matrix protein messenger RNA in HDPCs. Blockage of the JNK pathway in HDPCs decreases but does not completely abolish the cell migration and differentiation capacity induced by WNT6.
  
  
  CONCLUSIONS
  WNT6 activates the JNK signaling pathway in HDPCs, leading to migration and differentiation.
authors.affiliation: State Key Laboratory of Oral Diseases West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Ruimin
authors.initials: R
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oral Diseases West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oral Diseases West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Tong
authors.affiliation: State Key Laboratory of Oral Diseases West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Su
authors.affiliation: State Key Laboratory of Oral Diseases West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Oral Diseases West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Xuedong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oral Diseases West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China. Electronic address: yeling@scu.edu.cn.
authors.forename: Ling
authors.initials: L
authors.lastname: Ye
mesh_terms: D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000032:analysis; D000873:Anthracenes / Q000494:pharmacology; D002113:Calcification, Physiologic / Q000502:physiology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000032:analysis; D017077:Culture Media, Conditioned; D003782:Dental Pulp / Q000166:cytology*; D016326:Extracellular Matrix Proteins / Q000032:analysis; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009804:Odontoblasts / Q000502:physiology; D010750:Phosphoproteins / Q000032:analysis; D012795:Sialoglycoproteins / Q000032:analysis; D051153:Wnt Proteins / Q000502:physiology*; D055815:Young Adult; D000099311:Dentin Sialophosphoprotein
chemical_list: D000469:Alkaline Phosphatase; D000873:Anthracenes; D050659:Core Binding Factor Alpha 1 Subunit; D017077:Culture Media, Conditioned; D016326:Extracellular Matrix Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D051153:Wnt Proteins; D000099311:Dentin Sialophosphoprotein; C513309:DMP1 protein, human; C493709:RUNX2 protein, human; C490674:WNT6 protein, human; C432165:pyrazolanthrone
keywords: Cell differentiation; WNT6; c-Jun N-terminal kinase; cell migration; human dental pulp cells