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17β-Estradiol induces odontoblastic differentiation via activation of the c-Src/MAPK pathway in human dental pulp cells
- Source :
- Biochemistry and Cell Biology. 93:587-595
- Publication Year :
- 2015
- Publisher :
- Canadian Science Publishing, 2015.
-
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.
- Subjects :
- MAPK/ERK pathway
medicine.medical_specialty
Cell Survival
MAP Kinase Signaling System
Cellular differentiation
Proto-Oncogene Proteins pp60(c-src)
Biochemistry
Estrogen Receptor Antagonists
Calcification, Physiologic
stomatognathic system
Internal medicine
medicine
Humans
Phosphorylation
Protein Kinase Inhibitors
Molecular Biology
Dental Pulp
Cell Line, Transformed
Cell Proliferation
Estradiol
Odontoblasts
biology
Chemistry
Cell growth
Estrogen Receptor alpha
Gene Expression Regulation, Developmental
Cell Differentiation
Estrogens
Cell Biology
Cell biology
stomatognathic diseases
Odontoblast
Endocrinology
Mitogen-activated protein kinase
Dentin
biology.protein
Protein Processing, Post-Translational
Estrogen receptor alpha
Biomarkers
Proto-oncogene tyrosine-protein kinase Src
Subjects
Details
- ISSN :
- 12086002 and 08298211
- Volume :
- 93
- Database :
- OpenAIRE
- Journal :
- Biochemistry and Cell Biology
- Accession number :
- edsair.doi.dedup.....31ea399d9e85645b43c993facd834678