DLX3 Inhibits the Proliferation of Human Dental Pulp Cells Through Inactivation of Canonical Wnt/β-Catenin Signaling Pathway
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 rema...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-11-01
|
| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2018.01637/full |
| _version_ | 1811327441782702080 |
|---|---|
| author | Yunyan Zhan Xiaoyan Li Xiaoyan Li Xiaohui Gou Guohua Yuan Mingwen Fan Guobin Yang |
| author_facet | Yunyan Zhan Xiaoyan Li Xiaoyan Li Xiaohui Gou Guohua Yuan Mingwen Fan Guobin Yang |
| author_sort | Yunyan Zhan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T15:06:43Z |
| format | Article |
| id | doaj.art-9d7088af8c56495495746f7ee8564c87 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-13T15:06:43Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-9d7088af8c56495495746f7ee8564c872022-12-22T02:42:08ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-11-01910.3389/fphys.2018.01637405583DLX3 Inhibits the Proliferation of Human Dental Pulp Cells Through Inactivation of Canonical Wnt/β-Catenin Signaling PathwayYunyan Zhan0Xiaoyan Li1Xiaoyan Li2Xiaohui Gou3Guohua YuanMingwen Fan4Guobin Yang5The State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaShandong Provincial Key Laboratory of Oral Biomedicine, Department of Endodontics, School of Stomatology, Shandong University, Jinan, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaHomeodomain 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.https://www.frontiersin.org/article/10.3389/fphys.2018.01637/fullDKK1DLX3human dental pulp cellsproliferationWnt/β-catenin signaling |
| spellingShingle | Yunyan Zhan Xiaoyan Li Xiaoyan Li Xiaohui Gou Guohua Yuan Mingwen Fan Guobin Yang DLX3 Inhibits the Proliferation of Human Dental Pulp Cells Through Inactivation of Canonical Wnt/β-Catenin Signaling Pathway Frontiers in Physiology DKK1 DLX3 human dental pulp cells proliferation Wnt/β-catenin signaling |
| title | DLX3 Inhibits the Proliferation of Human Dental Pulp Cells Through Inactivation of Canonical Wnt/β-Catenin Signaling Pathway |
| title_full | DLX3 Inhibits the Proliferation of Human Dental Pulp Cells Through Inactivation of Canonical Wnt/β-Catenin Signaling Pathway |
| title_fullStr | DLX3 Inhibits the Proliferation of Human Dental Pulp Cells Through Inactivation of Canonical Wnt/β-Catenin Signaling Pathway |
| title_full_unstemmed | DLX3 Inhibits the Proliferation of Human Dental Pulp Cells Through Inactivation of Canonical Wnt/β-Catenin Signaling Pathway |
| title_short | DLX3 Inhibits the Proliferation of Human Dental Pulp Cells Through Inactivation of Canonical Wnt/β-Catenin Signaling Pathway |
| title_sort | dlx3 inhibits the proliferation of human dental pulp cells through inactivation of canonical wnt β catenin signaling pathway |
| topic | DKK1 DLX3 human dental pulp cells proliferation Wnt/β-catenin signaling |
| url | https://www.frontiersin.org/article/10.3389/fphys.2018.01637/full |
| work_keys_str_mv | AT yunyanzhan dlx3inhibitstheproliferationofhumandentalpulpcellsthroughinactivationofcanonicalwntbcateninsignalingpathway AT xiaoyanli dlx3inhibitstheproliferationofhumandentalpulpcellsthroughinactivationofcanonicalwntbcateninsignalingpathway AT xiaoyanli dlx3inhibitstheproliferationofhumandentalpulpcellsthroughinactivationofcanonicalwntbcateninsignalingpathway AT xiaohuigou dlx3inhibitstheproliferationofhumandentalpulpcellsthroughinactivationofcanonicalwntbcateninsignalingpathway AT guohuayuan dlx3inhibitstheproliferationofhumandentalpulpcellsthroughinactivationofcanonicalwntbcateninsignalingpathway AT mingwenfan dlx3inhibitstheproliferationofhumandentalpulpcellsthroughinactivationofcanonicalwntbcateninsignalingpathway AT guobinyang dlx3inhibitstheproliferationofhumandentalpulpcellsthroughinactivationofcanonicalwntbcateninsignalingpathway |