P75NTR−/− mice exhibit an alveolar bone loss phenotype and inhibited PI3K/Akt/β‐catenin pathway. (25th March 2020)

• Record Type: Journal Article
• Authors: Wang, Yingying; Yang, Kun; Li, Gang; Liu, Rui; Liu, Junyu; Li, Jun; Tang, Mengying; Zhao, Manzhu; Song, Jinlin; Wen, Xiujie
• Is Part Of: Cell proliferation. Volume 53:Number 4(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-03-25
• Subjects: Cell proliferation -- Periodicals; 571.84
• DOI: 10.1111/cpr.12800
• Languages: English
• ISSNs: 0960-7722

Abstract

Abstract: 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.