Back to Search
Start Over
Calcium-sensing receptor-ERK signaling promotes odontoblastic differentiation of human dental pulp cells.
- Source :
-
Bone [Bone] 2017 Aug; Vol. 101, pp. 191-201. Date of Electronic Publication: 2017 May 12. - Publication Year :
- 2017
-
Abstract
- Activation of the G protein-coupled calcium-sensing receptor (CaSR) has crucial roles in skeletal development and bone turnover. Our recent study has identified a role for activated CaSR in the osteogenic differentiation of human periodontal ligament stem cells. Furthermore, odontoblasts residing inside the tooth pulp chamber play a central role in dentin formation. However, it remains unclear how CaSR activation affects the odontoblastic differentiation of human dental pulp cells (HDPCs). We have investigated the odontoblastic differentiation of HDPCs exposed to elevated levels of extracellular calcium (Ca) and strontium (Sr), and the contribution of CaSR and the L-type voltage-dependent calcium channel (L-VDCC) to this process. Immunochemical staining of rat dental pulp tissue demonstrated that CaSR was expressed at high levels in the odontoblastic layer, moderate levels in the sublayer, and low levels in the central pulp tissue. Although normal HDPCs expressed low levels of CaSR, stimulation with Ca or Sr promoted both CaSR expression and odontoblastic differentiation of HDPCs along with increased expression of odontoblastic makers. These effects were inhibited by treatment with a CaSR antagonist, whereas treatment with an L-VDCC inhibitor had no effect. Additionally, knockdown of CaSR with siRNA suppressed odontoblastic differentiation of Ca- and Sr-treated HDPCs. ERK1/2 phosphorylation was observed in Ca- and Sr-treated HDPCs, whereas CaSR antagonist treatment or CaSR knockdown blocked ERK1/2 phosphorylation. Furthermore, inhibition of ERK1/2 suppressed mineralization of Ca- and Sr-treated HDPCs. These results suggest that elevated concentrations of extracellular Ca and Sr induce odontoblastic differentiation of HDPCs through CaSR activation and the ERK1/2 phosphorylation.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Cell Differentiation drug effects
Cells, Cultured
Female
Fluoroimmunoassay
Humans
Immunohistochemistry
Male
Naphthalenes pharmacology
Osteogenesis drug effects
Receptors, Calcium-Sensing antagonists & inhibitors
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction drug effects
Thiophenes pharmacology
Young Adult
Dental Pulp cytology
Odontoblasts cytology
Odontoblasts drug effects
Receptors, Calcium-Sensing metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2763
- Volume :
- 101
- Database :
- MEDLINE
- Journal :
- Bone
- Publication Type :
- Academic Journal
- Accession number :
- 28506888
- Full Text :
- https://doi.org/10.1016/j.bone.2017.05.012