title: Effects of leukemia inhibitory factor on proliferation and odontoblastic differentiation of human dental pulp cells.
abstract: BACKGROUND
  The purpose of this study was to determine whether the leukemia inhibitory factor (LIF) is expressed in human dental tissue and exerts its effect on proliferation and odontoblastic differentiation of the dental pulp cells (DPCs).
  
  
  METHODS
  An immunohistochemical assay was used to detect the expression of LIF and leukemia inhibitory factor receptor (LIFR) in the human dental pulp. The proliferation of DPCs was examined by culturing human primary DPCs in the presence of LIF with different doses or the neutralizing antibody to LIF. Western blot was performed to assay the phosphorylation of Janus kinase 2 (Jak2) and signal transducer and activator of transcription 3 (Stat3) in the presence or absence of LIF and/or AG 490, a specific inhibitor of Jak2. The odontoblastic differentiation of DPCs was determined using the alkaline phosphatase (ALP) activity assay, quantification of bone sialoprotein (BSP) and dentin sialophosphoprotein (DSPP) gene expression, and mineralization nodule formation.
  
  
  RESULTS
  LIF and LIFR were present in the odontoblasts and DPCs. LIF induced proliferation of DPCs, which was inhibited by the LIF neutralizing antibody and AG 490. LIF induced phosphorylation of Jak2 and Stat3 but not in the presence of the AG490. ALP activity of DPCs, in the absence or presence of mineralization induction medium, was inhibited by LIF. Furthermore, the mineralization nodule formation and the expression of BSP and DSPP were inhibited by LIF. This inhibition on differentiation was attenuated by the AG490.
  
  
  CONCLUSIONS
  LIF and LIFR are expressed in the human dental pulp. LIF promotes the proliferation of DPCs, and the odontoblastic differentiation is inhibited via the Jak2-Stat3 signaling pathway.
authors.affiliation: Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan City, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Mingbo
authors.initials: M
authors.lastname: Qian
authors.forename: Youde
authors.initials: Y
authors.lastname: Liang
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Yining
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000469:Alkaline Phosphatase / Q000032:analysis; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D015153:Blotting, Western; D002113:Calcification, Physiologic / Q000502:physiology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002648:Child; D003782:Dental Pulp / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D058574:Integrin-Binding Sialoprotein / Q000032:analysis; D053614:Janus Kinase 2 / Q000032:analysis / Q000037:antagonists & inhibitors; D053605:Leukemia Inhibitory Factor / Q000032:analysis / Q000502:physiology*; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit / Q000032:analysis / Q000502:physiology; D009804:Odontoblasts / Q000166:cytology*; D010750:Phosphoproteins / Q000032:analysis; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000032:analysis; D012795:Sialoglycoproteins / Q000032:analysis; D020032:Tyrphostins / Q000494:pharmacology; D000099311:Dentin Sialophosphoprotein
chemical_list: D000469:Alkaline Phosphatase; D057134:Antibodies, Neutralizing; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D058574:Integrin-Binding Sialoprotein; D053614:Janus Kinase 2; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D010750:Phosphoproteins; D050796:STAT3 Transcription Factor; D012795:Sialoglycoproteins; D020032:Tyrphostins; D000099311:Dentin Sialophosphoprotein; C507840:LIFR protein, human; C494086:STAT3 protein, human; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C507924:JAK2 protein, human