Hypoxia-inducible factor 1α induces osteo/odontoblast differentiation of human dental pulp stem cells via Wnt/β-catenin transcriptional cofactor BCL9.
Animals
Calcification, Physiologic
/ genetics
Cell Differentiation
/ genetics
Cells, Cultured
Dental Pulp
/ cytology
Gene Expression
/ genetics
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
/ genetics
Mice
Odontoblasts
/ physiology
Signal Transduction
/ genetics
Stem Cells
/ physiology
Transcription Factors
/ genetics
Wnt Proteins
/ metabolism
beta Catenin
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
13 01 2022
13 01 2022
Historique:
received:
12
07
2021
accepted:
14
12
2021
entrez:
14
1
2022
pubmed:
15
1
2022
medline:
1
3
2022
Statut:
epublish
Résumé
Accelerated dental pulp mineralization is a common complication in avulsed/luxated teeth, although the mechanisms underlying this remain unclear. We hypothesized that hypoxia due to vascular severance may induce osteo/odontoblast differentiation of dental pulp stem cells (DPSCs). This study examined the role of B-cell CLL/lymphoma 9 (BCL9), which is downstream of hypoxia-inducible factor 1α (HIF1α) and a Wnt/β-catenin transcriptional cofactor, in the osteo/odontoblastic differentiation of human DPSCs (hDPSCs) under hypoxic conditions. hDPSCs were isolated from extracted healthy wisdom teeth. Hypoxic conditions and HIF1α overexpression induced significant upregulation of mRNAs for osteo/odontoblast markers (RUNX2, ALP, OC), BCL9, and Wnt/β-catenin signaling target genes (AXIN2, TCF1) in hDPSCs. Overexpression and suppression of BCL9 in hDPSCs up- and downregulated, respectively, the mRNAs for AXIN2, TCF1, and the osteo/odontoblast markers. Hypoxic-cultured mouse pulp tissue explants showed the promotion of HIF1α, BCL9, and β-catenin expression and BCL9-β-catenin co-localization. In addition, BCL9 formed a complex with β-catenin in hDPSCs in vitro. This study demonstrated that hypoxia/HIF1α-induced osteo/odontoblast differentiation of hDPSCs was partially dependent on Wnt/β-catenin signaling, where BCL9 acted as a key mediator between HIF1α and Wnt/β-catenin signaling. These findings may reveal part of the mechanisms of dental pulp mineralization after traumatic dental injury.
Identifiants
pubmed: 35027586
doi: 10.1038/s41598-021-04453-8
pii: 10.1038/s41598-021-04453-8
pmc: PMC8758693
doi:
Substances chimiques
BCL9 protein, human
0
HIF1A protein, human
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Transcription Factors
0
Wnt Proteins
0
beta Catenin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
682Subventions
Organisme : Japan Society for the Promotion of Science
ID : #21K09870
Organisme : Japan Society for the Promotion of Science
ID : #18K17039
Organisme : Japan Society for the Promotion of Science
ID : #20K18499
Organisme : Japan Society for the Promotion of Science
ID : #20K18526
Organisme : Japan Society for the Promotion of Science
ID : #19K24136
Organisme : Japan Society for the Promotion of Science
ID : #20K18496
Organisme : Japan Society for the Promotion of Science
ID : #21K16989
Organisme : Japan Society for the Promotion of Science
ID : #21K09911-1
Informations de copyright
© 2022. The Author(s).
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