Bone marrow mesenchymal stem cell exosomes improve fracture union via remodeling metabolism in nonunion rat model

Abstract Background Nonunion of fractures is a major unsolved problem in clinical treatment and prognosis of orthopedics. Bone marrow mesenchymal stem cell (BMSC) exosomes have been proven to be involved in mediating tissue and bone regeneration in a variety of diseases. However, the role of BMSC ex...

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Main Authors: Cheng Li, Ming Chen, Lijun Guo, Dadong Yu, Zhonghai Xu, Bin Chen, Zhijian Xiao
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Journal of Orthopaedic Surgery and Research
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Online Access:https://doi.org/10.1186/s13018-025-05721-3
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Summary:Abstract Background Nonunion of fractures is a major unsolved problem in clinical treatment and prognosis of orthopedics. Bone marrow mesenchymal stem cell (BMSC) exosomes have been proven to be involved in mediating tissue and bone regeneration in a variety of diseases. However, the role of BMSC exosomes in fracture nonunion is unclear. Methods BMSC exosomes were injected into a rat model of nonunion fracture, and the fracture-healing site was detected by micro-CT and the serum metabolites were analyzed by LC-MS/MS. Results The results showed that the exosomes could be successfully isolated from rat BMSCs cultured in an exosome-free medium. Compared with the model group, the fracture site of the exosome-treated rats were healing obviously. Compared with the PBS group, there were 158 up-regulated differential abundance metabolites (DAMs) and 79 down-regulated DAMs in the BMSC-exo group. The DAMs were enriched in ‘Th1 and Th2 cell differentiation’, ‘ErbB signaling pathway’, ‘PPAR signaling pathway’ and ‘HIF-1 signaling pathway’ that were related to the function of cell proliferation and differentiation. DAMs-PE in HIF-1 signaling pathway were the major metabolite to promote fracture healing. Conclusions Our study reveals the mechanism by which BMSC-exosome improves the fracture healing process through metabolic reprogramming and provides a reference for the treatment of fracture nonunion.
ISSN:1749-799X