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Updated: Dec 25, 2025
Author Spotlight: Comparing Alveolar and Long Bone Remodeling to Explore OTM Model Potential
Published on: July 21, 2023
p75NTR-/- mice exhibit an alveolar bone loss phenotype and inhibited PI3K/Akt/β-catenin pathway
Yingying Wang1, Kun Yang2, Gang Li1
1Department of Stomatology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
Objectives:
The aim of this study was to investigate the role of p75 neurotrophin receptor (p75NTR) in regulating the mouse alveolar bone development and the mineralization potential of murine ectomesenchymal stem cells (EMSCs). Moreover, we tried to explore the underlying mechanisms associated with the PI3K/Akt/β-catenin pathway.
Materials And Methods:
p75NTR knockout (p75NTR-/- ) mice and wild-type (WT) littermates were used. E12.5d p75NTR-/- and WT EMSCs were isolated in the same pregnant p75NTR-/+ mice from embryonic maxillofacial processes separately. Mouse alveolar bone mass was evaluated using micro-CT. Differential osteogenic differentiation pathways between p75NTR-/- and WT EMSCs were analysed by RNA-sequencing. The PI3K inhibitor LY294002 and PI3K agonist 740Y-P were used to regulate the PI3K/Akt pathway in EMSCs. p75NTR overexpression lentiviruses, p75NTR knock-down lentiviruses and recombined mouse NGF were used to transfect cells.
Results:
The alveolar bone mass was found reduced in the p75NTR knockout mouse comparing to the WT mouse. During mineralization induction, p75NTR-/- EMSCs displayed decreased osteogenic capacity and downregulated PI3K/Akt/β-catenin signalling. The PI3K/Akt/β-catenin pathway positively regulates the potential of differential mineralization in EMSCs. The promotive effect of p75NTR overexpression can be attenuated by LY294002, while the inhibitory effect of p75NTR knock-down on Runx2 and Col1 expression can be reversed by 740Y-P.
Conclusion:
Deletion of p75NTR reduced alveolar bone mass in mice. P75NTR positively regulated the osteogenic differentiation of EMSCs via enhancing the PI3K/Akt/β-catenin pathway.
Insights
The p75 neurotrophin receptor (p75NTR) is crucial for mouse alveolar bone development. Deleting p75NTR reduces bone mass and impairs ectomesenchymal stem cell mineralization by downregulating the PI3K/Akt/β-catenin pathway.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Bone Biology
Background:
- The p75 neurotrophin receptor (p75NTR) plays a role in neural development and survival.
- Its function in bone development and stem cell differentiation is not fully understood.
Purpose of the Study:
- To investigate the role of p75NTR in mouse alveolar bone development.
- To explore the effect of p75NTR on murine ectomesenchymal stem cells (EMSCs) mineralization potential.
- To elucidate the involvement of the PI3K/Akt/β-catenin pathway.
Main Methods:
- Utilized p75NTR knockout (p75NTR-/-) and wild-type (WT) mice.
- Isolated EMSCs from embryonic maxillofacial processes for in vitro studies.
- Assessed alveolar bone mass using micro-CT and analyzed gene expression via RNA-sequencing.
- Manipulated the PI3K/Akt pathway using inhibitors and agonists, and altered p75NTR levels through lentiviral transfection.
Main Results:
- p75NTR-/- mice exhibited reduced alveolar bone mass compared to WT littermates.
- p75NTR-/- EMSCs showed diminished osteogenic capacity and downregulated PI3K/Akt/β-catenin signaling during mineralization.
- The PI3K/Akt/β-catenin pathway was identified as a positive regulator of EMSC mineralization potential.
Conclusions:
- Deletion of p75NTR negatively impacts alveolar bone mass in mice.
- p75NTR positively regulates osteogenic differentiation of EMSCs by enhancing the PI3K/Akt/β-catenin pathway.
