The Hippo-YAP/β-catenin signaling axis coordinates odontogenic differentiation in dental pulp stem cells: Implications for dentin-pulp regeneration.
<h4>Objective</h4>This study investigated the interplay between Hippo-YAP and β-catenin signaling in regulating odontogenic differentiation of human dental pulp stem cells (DPSCs) and explored its potential implications for dentin-pulp regeneration.<h4>Methods</h4>Using lenti...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0326978 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | <h4>Objective</h4>This study investigated the interplay between Hippo-YAP and β-catenin signaling in regulating odontogenic differentiation of human dental pulp stem cells (DPSCs) and explored its potential implications for dentin-pulp regeneration.<h4>Methods</h4>Using lentivirus-mediated YAP overexpression/silencing, β-catenin siRNA knockdown, and pharmacological Wnt inhibition (via WIF-1), we assessed DPSC proliferation, migration, mineralization, and molecular markers (via qRT-PCR, immunofluorescence). In vivo validation employed subcutaneous transplantation of DPSC-seeded scaffolds in immunocompromised mice.<h4>Results</h4>YAP activation enhanced DPSC proliferation (1.44-fold), migration (1.39-fold), invasion (1.54-fold), and differentiation, as evidenced by elevated ALP activity (1.46-fold) and mineralization (1.36-fold). We observed transcriptional upregulation of odontogenic markers (RUNX2, DSPP, DMP1, OCN, ALP) and Wnt pathway components (β-catenin, Cyclin D1, c-Myc). Immunofluorescence revealed coordinated YAP and β-catenin expression patterns during differentiation. β-catenin silencing or Wnt inhibition abolished YAP-mediated functional enhancements and simultaneously suppressed YAP expression, partially confirming bidirectional regulation. In vivo, YAP-overexpressing DPSCs exhibited 1.27- to 1.62-fold induction of dentin-specific markers and β-catenin, whereas YAP silencing impaired these markers expression.<h4>Conclusions</h4>Our findings demonstrate that coordinated YAP and β-catenin signaling drives DPSC odontogenesis, with potential implications for dentin regeneration. Although reciprocal regulation is evident, direct molecular interactions require further validation. |
|---|---|
| ISSN: | 1932-6203 |