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J Cell Physiol. 2019 Jul 5. doi: 10.1002/jcp.29034. [Epub ahead of print]

Parathyroid hormone enhances the osteo/odontogenic differentiation of dental pulp stem cells via ERK and P38 MAPK pathways.

Ge X1,2, Li Z1,2, Jing S2, Wang Y2, Li N1,2, Lu J1,2, Yu J2.

Author information

1
Key Laboratory of Oral Diseases of Jiangsu Province and Stomatological Institute of Nanjing Medical University, Nanjing, Jiangsu, China.
2
Endodontic Department, School of Stomatology, Nanjing Medical University, Nanjing, Jiangsu, China.

Abstract

OBJECTIVE:

Parathyroid hormone (PTH) is a main systemic mediator of calcium and phosphate homeostasis in the bone. Dental pulp stem cells (DPSCs) have been extensively studied in the regeneration of bone and tooth tissues. This paper aims to uncover the influences of PTH on the proliferative ability and osteo/odontogenic differentiation of DPSCs, as well as the underlying mechanisms.

MATERIALS AND METHODS:

The optimal concentration of PTH on DPSCs was determined by alkaline phosphatase (ALP) activity assay, ALP staining and western blot analysis. Proliferative ability and cell cycle distribution of DPSCs were analyzed by Cell counting kit-8, 5-ethynyl-20-deoxyuridine assay, and flow cytometry. Osteo/odontogenic capacity of DPSCs was evaluated and finally, the involvement of mitogen-activated protein kinase (MAPK) pathway was assessed.

RESULTS:

Purified DPSCs were obtained by enzymatic digestion, which presented a typical fibroblast-like morphology. 10-9  mol/L PTH was concerned as the optimal concentration for DPSCs induction. 10-9  mol/L PTH treatment did not change the proliferative rate of DPSCs (p > .05). Relative expressions of DSPP/DSPP, RUNX2/RUNX2, OSX/OSX, and ALP/ALP were upregulated in PTH-treated DPSCs relative to control group. Particularly, their mRNA/protein levels at Day 7 were markedly higher relative to those at Day 3 (p < .05 or p < .01). Mineralized nodules were formed after PTH induction, and calcium content increased by cetylpyridinium chloride quantitative analysis. Mechanistically, the protein levels of p-ERK and p-P38 significantly increased after PTH treatment, and the inhibitors targeting MAPK were identified that weakened the effects of PTH on the committed differentiation of DPSCs.

CONCLUSIONS:

PTH enhances the osteo/odontogenic differentiation capacity of DPSCs via ERK and P38 signaling pathways.

KEYWORDS:

dental pulp stem cells; differentiation; mitogen-activated protein kinase; parathyroid hormone

PMID:
31276209
DOI:
10.1002/jcp.29034

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