title: Adrenomedullin Promotes the Proliferation and Inhibits Apoptosis of Dental Pulp Stem Cells Involved in Divergence Pathways.
abstract: BACKGROUND
  Adrenomedullin (ADM) is highly expressed in dental tissues at the critical developmental time points during tooth development. However, its role in pulp repair and pulp injury is still unknown. The study aimed to investigate the mechanisms by which ADM affects the proliferation and apoptosis of human dental pulp stem cells (DPSCs).
  
  
  METHODS
  Fifty-four freshly extracted wisdom teeth were obtained from 27 patients with caries and 27 without. Enzyme-linked immunosorbent assay and immunohistochemistry were used to examine the expression levels of ADM in caries and normal pulp tissues. Human primary DPSCs from the third passage were incubated with ADM (10(-8) mol/L) for 24 hours; the cell cycle and apoptosis were investigated by flow cytomery, and protein expression was investigated using Western blot analysis.
  
  
  RESULTS
  The levels of ADM in caries pulp tissues were significantly higher than those in normal pulp tissues. Incubation with ADM enhanced the percentage of G2/S/M phase DPSCs (P < .01) by the addition of a JNK/c-Jun inhibitor. Incubation with ADM reduced DPSC apoptosis by the addition of the Src/glycogen synthase kinase-3 inhibitor. ADM also ameliorated CoCl2-induced apoptosis and caspase-3 expression.
  
  
  CONCLUSIONS
  ADM enhances the proliferation of DPSCs through activation of the JNK/c-Jun signaling pathway and inhibits apoptosis of DPSCs through activation of the Src/glycogen synthase kinase-3 signaling pathway.
authors.affiliation: Department of Stomatology, Third Military Medical University, Xinqiao Hospital, Chongqing, China; Department of Stomatology, Second Military Medical University, Changhai Hospital, Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Stomatology, Second Military Medical University, Changhai Hospital, Shanghai, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Tian
authors.affiliation: Department of Stomatology, Second Military Medical University, Changhai Hospital, Shanghai, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Stomatology, Second Military Medical University, Changhai Hospital, Shanghai, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Stomatology, Third Military Medical University, Xinqiao Hospital, Chongqing, China. Electronic address: tanyinghui2015@163.com.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Tan
mesh_terms: D000293:Adolescent; D053607:Adrenomedullin / Q000502:physiology*; D000328:Adult; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D049109:Cell Proliferation / Q000502:physiology; D003782:Dental Pulp / Q000166:cytology* / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D055815:Young Adult
chemical_list: D053607:Adrenomedullin; D016392:Proto-Oncogene Proteins pp60(c-src); D038362:Glycogen Synthase Kinase 3
keywords: Adrenomedullin; apoptosis; proliferation; pulp stem cells