title: Calcium Hydroxide-induced Proliferation, Migration, Osteogenic Differentiation, and Mineralization via the Mitogen-activated Protein Kinase Pathway in Human Dental Pulp Stem Cells.
abstract: BACKGROUND
  Calcium hydroxide has been extensively used as the gold standard for direct pulp capping in clinical dentistry. It induces proliferation, migration, and mineralization in dental pulp stem cells (DPSCs), but the underlying mechanisms are still unclear. The aim of this study was to investigate the role of the mitogen-activated protein (MAP) kinase pathway in calcium hydroxide-induced proliferation, migration, osteogenic differentiation, and mineralization in human DPSCs.
  
  
  METHODS
  Human DPSCs between passages 3 and 6 were used. DPSCs were preincubated with inhibitors of MAP kinases and cultured with calcium hydroxide. The phosphorylated MAP kinases were detected by Western blot analysis. Cell viability was analyzed via the methylthiazol tetrazolium assay. Cell migration was estimated using the wound healing assay. Alkaline phosphatase (ALP) expression was analyzed using the ALP staining assay. Mineralization was studied by alizarin red staining analysis.
  
  
  RESULTS
  Calcium hydroxide significantly promoted the phosphorylation of the c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase. The inhibition of JNK and p38 signaling abolished calcium hydroxide-induced proliferation of DPSCs. The inhibition of JNK, p38, and extracellular signal-regulated kinase signaling suppressed the migration, ALP expression, and mineralization of DPSCs.
  
  
  CONCLUSIONS
  Our study showed that the MAP kinase pathway was involved in calcium hydroxide-induced proliferation, migration, osteogenic differentiation, and mineralization in human DPSCs.
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
authors.forename: Luoping
authors.initials: L
authors.lastname: Chen
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, China. Electronic address: lishazheng@buaa.edu.cn.
authors.forename: Lisha
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
authors.forename: Jinpeng
authors.initials: J
authors.lastname: Gui
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ji
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, China; National Research Center for Rehabilitation Technical Aids, Beijing, China. Electronic address: yubofan@buaa.edu.cn.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Fan
mesh_terms: D000293:Adolescent; D000469:Alkaline Phosphatase / Q000378:metabolism; D015153:Blotting, Western; D002113:Calcification, Physiologic / Q000187:drug effects*; D002126:Calcium Hydroxide / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003782:Dental Pulp / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects*; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D000469:Alkaline Phosphatase; D002126:Calcium Hydroxide
keywords: Calcium hydroxide; dental pulp stem cells; migration; mineralization; proliferation