DLX3 Inhibits the Proliferation of Human Dental Pulp Cells Through Inactivation of Canonical Wnt/β-Catenin Signaling Pathway

Bibliographic Details
Title: DLX3 Inhibits the Proliferation of Human Dental Pulp Cells Through Inactivation of Canonical Wnt/β-Catenin Signaling Pathway
Authors: Yunyan Zhan, Xiaoyan Li, Xiaohui Gou, Guohua Yuan, Mingwen Fan, Guobin Yang
Source: Frontiers in Physiology, Vol 9 (2018)
Publisher Information: Frontiers Media S.A., 2018.
Publication Year: 2018
Collection: LCC:Physiology
Subject Terms: DKK1, DLX3, human dental pulp cells, proliferation, Wnt/β-catenin signaling, Physiology, QP1-981
More Details: Homeodomain gene Distal-less-3 (Dlx3) plays an important role during tooth development. Our previous studies indicate that DLX3 inhibits proliferation of human dental pulp cells (hDPCs). However, the mechanism of DLX3 regulating proliferation of hDPCs and maintaining the quiescence of the cells remain unknown. Given the importance of canonical Wnt signaling in the proliferation of dental pulp cell and tooth development, we hypothesized that DLX3 inhibited proliferation of hDPCs through inactivation of canonical Wnt signaling. With overexpression or knock-down of DLX3 in primary hDPCs, we found DLX3 down regulated canonical Wnt signaling and its downstream target genes. And when the DLX3 overexpressed-cells were treated with lithium chloride, the proliferation inhibition by DLX3 was reversed. We also found that DLX3 enhanced the expression of DKK1 and the reduced proliferation of hDPCs by DLX3 was reversed with knock-down of DKK1. Furthermore, luciferase reporter assay and chromatin immunoprecipitation assay showed DLX3 was able to bind to Dkk1 promoter region from nucleotides (nt) -1656 to -1245, and stimulated Dkk1 promoter activity. Mutagenesis studies further revealed two DLX3 responsive elements in Dkk1 promoter. Taken together, our data indicate that DLX3 inhibits proliferation of hDPCs via inactivation of Wnt/β-catenin signaling pathway by directly binding to Dkk1 promoter and increasing its expression.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1664-042X
Relation: https://www.frontiersin.org/article/10.3389/fphys.2018.01637/full; https://doaj.org/toc/1664-042X
DOI: 10.3389/fphys.2018.01637
Access URL: https://doaj.org/article/9d7088af8c56495495746f7ee8564c87
Accession Number: edsdoj.9d7088af8c56495495746f7ee8564c87
Database: Directory of Open Access Journals
More Details
ISSN:1664042X
DOI:10.3389/fphys.2018.01637
Published in:Frontiers in Physiology
Language:English