A WWP2-PTEN-KLF5 signaling axis regulates odontoblast differentiation and dentinogenesis in mice.
Animals
Cell Differentiation
Dentin
/ metabolism
Dentinogenesis
Extracellular Matrix Proteins
/ genetics
Kruppel-Like Transcription Factors
/ genetics
Mice
Mice, Knockout
Odontoblasts
/ metabolism
PTEN Phosphohydrolase
/ genetics
Phosphoproteins
/ metabolism
Sialoglycoproteins
/ metabolism
Signal Transduction
Transcription Factors
/ metabolism
Ubiquitin-Protein Ligases
/ genetics
Krüppel-like factor 5
WW domain-containing E3 Ubiquitin-protein ligase 2
dentin
differentiation
odontoblasts
phosphatase and tensin homolog
tooth development
ubiquitination
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
22
03
2022
revised:
20
06
2022
accepted:
22
06
2022
pubmed:
6
7
2022
medline:
9
9
2022
entrez:
5
7
2022
Statut:
ppublish
Résumé
WW domain-containing E3 Ubiquitin-protein ligase 2 (WWP2) has been found to positively regulate odontoblastic differentiation by monoubiquitinating the transcription factor Kruppel-like factor 5 (KLF5) in a cell culture system. However, the in vivo role of WWP2 in mouse teeth remains unknown. To explore this, here we generated Wwp2 knockout (Wwp2 KO) mice. We found that molars in Wwp2 KO mice exhibited thinner dentin, widened predentin, and reduced numbers of dentinal tubules. In addition, expression of the odontoblast differentiation markers Dspp and Dmp1 was decreased in the odontoblast layers of Wwp2 KO mice. These findings demonstrate that WWP2 may facilitate odontoblast differentiation and dentinogenesis. Furthermore, we show for the first time that phosphatase and tensin homolog (PTEN), a tumor suppressor, is expressed in dental papilla cells and odontoblasts of mouse molars and acts as a negative regulator of odontoblastic differentiation. Further investigation indicated that PTEN is targeted by WWP2 for degradation during odontoblastic differentiation. We demonstrate PTEN physically interacts with and inhibits the transcriptional activity of KLF5 on Dspp and Dmp1. Finally, we found WWP2 was able to suppress the interaction between PTEN and KLF5, which diminished the inhibition effect of PTEN on KLF5. Taken together, this study confirms the essential role of WWP2 and the WWP2-PTEN-KLF5 signaling axis in odontoblast differentiation and dentinogenesis in vivo.
Identifiants
pubmed: 35780838
pii: S0021-9258(22)00662-7
doi: 10.1016/j.jbc.2022.102220
pmc: PMC9358474
pii:
doi:
Substances chimiques
Dmp1 protein, mouse
0
Extracellular Matrix Proteins
0
Klf5 protein, mouse
0
Kruppel-Like Transcription Factors
0
Phosphoproteins
0
Sialoglycoproteins
0
Transcription Factors
0
dentin sialophosphoprotein
0
Wwp2 protein, mouse
EC 2.3.2.26
Ubiquitin-Protein Ligases
EC 2.3.2.27
PTEN Phosphohydrolase
EC 3.1.3.67
Pten protein, mouse
EC 3.1.3.67
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102220Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.