title: 17β-Estradiol induces odontoblastic differentiation via activation of the c-Src/MAPK pathway in human dental pulp cells.
abstract: The present study is aimed at investigating the effects of the exogenous estrogen 17β-estradiol (E2) on odontoblastic differentiation in human dental pulp cells (HDPCs) immotalized with hTERT gene and their molecular mechanism. Proliferation was detected by BrdU assay, and odontoblast differentiation induction was evaluated by the expression of dentin sialophosphoprotein (DSPP), dentin sialoprotein (DSP) and dentin matrix protein1 (DMP1), and alkaline phosphatase (ALP) activity and mineralization. Estrogen receptor-α (ER-α), c-Src, and mitogen-activated protein kinases (MAPKs) were examined and their inhibitors were used to determine the roles on odontogenic induction. E2 significantly promoted the HDPC proliferation, which was mediated by extracellular signal-related kinase 1/2. E2 upregulated DSPP, DSP, and DMP1 as the odontogenic differentiation markers and enhanced ALP activity and mineralization. E2 increased phosphorylation of ER-α and fulvestrant, an ER downregulator, significantly downregulated DSPP, DMP1, and DSP induced by E2. Moreover, E2 treatment activated c-Src and MAPKs upon odontogenic induction, whereas chemical inhibition of c-Src and MAPKs decreased expression of DSPP, DMP1, and DSP and mineralization augmented by E2. Moreover, fulvestrant reduced E2-induced phosphorylation of c-Src and MAPK and inhibition of c-Src by PP2 attenuated activation of MAPKs during E2-induced odontoblastic differentiation. Taken together, these results indicated that E2 stimulates odontoblastic differentiation of HDPCs via coordinated regulation of ER-α, c-Src, and MAPK signaling pathways, which may play a key role in the regeneration of dentin.
authors.affiliation: a Department of Oral Physiology, School of Dentistry, Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, Chonnam National University, Gwangju 61186, South Korea.
authors.forename: Su Mi
authors.initials: SM
authors.lastname: Woo
authors.affiliation: a Department of Oral Physiology, School of Dentistry, Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, Chonnam National University, Gwangju 61186, South Korea.
authors.forename: Kyung Joo
authors.initials: KJ
authors.lastname: Seong
authors.affiliation: b School of Biological Sciences and Technology, Chonnam National University, Gwangju 61186, South Korea.
authors.forename: Sang Jin
authors.initials: SJ
authors.lastname: Oh
authors.affiliation: c Department of Oral and Maxillofacial Surgery, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju 61186, South Korea.
authors.forename: Hong Ju
authors.initials: HJ
authors.lastname: Park
authors.affiliation: d Department of Oral Anatomy, School of Dentistry, Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, Chonnam National University, Gwangju 61186, South Korea.
authors.forename: Sun Hun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: a Department of Oral Physiology, School of Dentistry, Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, Chonnam National University, Gwangju 61186, South Korea.
authors.forename: Won Jae
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: a Department of Oral Physiology, School of Dentistry, Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, Chonnam National University, Gwangju 61186, South Korea.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Jung
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003804:Dentin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000737:chemistry / Q000494:pharmacology*; D065171:Estrogen Receptor Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009804:Odontoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000737:chemistry / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C506487:ESR1 protein, human; D065171:Estrogen Receptor Antagonists; D047628:Estrogen Receptor alpha; D004967:Estrogens; D047428:Protein Kinase Inhibitors; D004958:Estradiol; D016392:Proto-Oncogene Proteins pp60(c-src)
keywords: 17β-estradiol; c-Src; cellules de pulpe dentaire humaines; différenciation odontogénique; estradiol; human dental pulp cells; kinases activées par les mitogènes (MAPK); mitogen-activated protein kinase; odontogenic differentiation