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Journal of Orthopaedic Surgery and Research

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Open Access 01-12-2024 | Fracture Healing | Research article

Silencing p75NTR regulates osteogenic differentiation and angiogenesis of BMSCs to enhance bone healing in fractured rats

Authors: Zhifeng Wu, Yongming Yang, Ming Wang

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2024

Abstract

Background

Fractures heal through a process that involves angiogenesis and osteogenesis but may also lead to non-union or delayed healing. Bone marrow mesenchymal stem cells (BMSCs) have been reported to play a pivotal role in bone formation and vascular regeneration and the p75 neurotrophin receptor (p75NTR) as being an important regulator of osteogenesis. Herein, we aim to determine the potential mediation of BMSCs by p75NTR in bone healing.

Methods

Rat BMSCs were identified by flow cytometry (FCM) to detect cell cycle and surface markers. Then transfection of si/oe-p75NTR was performed in BMSCs, followed by Alizarin red staining to detect osteogenic differentiation of cells, immunofluorescence double staining was performed to detect the expression of p75NTR and sortilin, co-immunoprecipitation (CO-IP) was conducted to analyze the interaction between p75NTR and sortilin, and EdU staining and cell scratch assay to assess the proliferation and migration of human umbilical vein endothelial cells (HUVECs). The expression of HIF-1α, VEGF, and apoptosis-related proteins were also detected. In addition, a rat fracture healing model was constructed, and BMSCs-si-p75NTR were injected, following which the fracture condition was observed using micro-CT imaging, and the expression of platelet/endothelial cell adhesion molecule-1 (CD31) was assessed.

Results

The results showed that BMSCs were successfully isolated, p75NTR inhibited apoptosis and the osteogenic differentiation of BMSCs, while si-p75NTR led to a decrease in sortilin expression in BMSCs, increased proliferation and migration in HUVECs, and upregulation of HIF-1α and VEGF expression. In addition, an interaction was observed between p75NTR and sortilin. The knockdown of p75NTR was found to reduce the severity of fracture in rats and increase the expression of CD31 and osteogenesis-related proteins.

Conclusion

Silencing p75NTR effectively modulates BMSCs to promote osteogenic differentiation and angiogenesis, offering a novel perspective for improving fracture healing.

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Title: Silencing p75NTR regulates osteogenic differentiation and angiogenesis of BMSCs to enhance bone healing in fractured rats
Authors: Zhifeng Wu
Yongming Yang
Ming Wang
Publication date: 01-12-2024
Publisher: BioMed Central
Keyword: Fracture Healing
Published in: Journal of Orthopaedic Surgery and Research / Issue 1/2024
Electronic ISSN: 1749-799X
DOI: https://doi.org/10.1186/s13018-024-04653-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Silencing p75NTR regulates osteogenic differentiation and angiogenesis of BMSCs to enhance bone healing in fractured rats

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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