AKT from dental epithelium to papilla promotes odontoblast differentiation

Jiangyi Wang; Xiaoyu Lin; Zongshan Shen; Guoqing Li; Lei Hu; Qiong Li; Yang Li; Jinsong Wang; Chunmei Zhang; Songlin Wang; Xiaoshan Wu

doi:10.1016/j.diff.2023.10.002

AKT from dental epithelium to papilla promotes odontoblast differentiation

Differentiation. 2023 Nov-Dec:134:52-60. doi: 10.1016/j.diff.2023.10.002. Epub 2023 Oct 21.

Authors

Jiangyi Wang¹, Xiaoyu Lin¹, Zongshan Shen¹, Guoqing Li¹, Lei Hu², Qiong Li¹, Yang Li¹, Jinsong Wang³, Chunmei Zhang¹, Songlin Wang⁴, Xiaoshan Wu⁵

Affiliations

¹ Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China.
² Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China; Department of Prosthodontics, Capital Medical University School of Stomatology, Beijing, 100050, China.
³ Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences, Beijing, 100069, China.
⁴ Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China; Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences, Beijing, 100069, China; Academician Workstation for Oral-Maxillofacial Regenerative Medicine, Central South University, Changsha, 410008, China. Electronic address: slwang@ccmu.edu.cn.
⁵ Academician Workstation for Oral-Maxillofacial Regenerative Medicine, Central South University, Changsha, 410008, China; Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China. Electronic address: drwuxiaoshan@csu.edu.cn.

PMID: 37898102
DOI: 10.1016/j.diff.2023.10.002

Abstract

Epithelial-mesenchymal interactions occur during tooth development. The dental epithelium (DE) is regarded as the signal center that regulates tooth morphology. However, the mechanism by which DE regulates the differentiation of mesenchyme-derived dental papilla (DP) into odontoblasts remains unclear. Using miniature pigs as a model, we analyzed the expression profiles of the DE and DP during odontoblast differentiation using high-throughput RNA sequencing. The phosphatidylinositol-3-kinase (PI3K)/AKT pathway is one of the most enriched pathways in both DE and DP. The PI3K/AKT pathway was first activated in the inner enamel epithelium but not in the DP on embryonic day 50. This pathway was then activated in the odontoblast layer on embryonic day 60. We showed that AKT activation promoted odontoblast differentiation of DP cells. We further demonstrated that activation of PI3K/AKT signaling in the DE effectively increased the expression levels of AKT and dentin sialophosphoprotein in DP cells. Additionally, we found that DE cells secreted collagen type IV alpha 6 chain (COL4A6) downstream of epithelial AKT signaling to positively regulate mesenchymal AKT levels. Therefore, our data suggest that PI3K/AKT signaling from the DE to the DP promotes odontoblast differentiation via COL4A6 secretion.

Keywords: Cell differentiation; Cell interaction; Coculture; Dental papilla; Development; Tooth.

MeSH terms

Animals
Cell Differentiation / genetics
Epithelium
Odontoblasts* / metabolism
Phosphatidylinositol 3-Kinases / genetics
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt* / genetics
Proto-Oncogene Proteins c-akt* / metabolism
Swine

Substances

Proto-Oncogene Proteins c-akt
Phosphatidylinositol 3-Kinases