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

IF 2.8 3区医学 Q1 ORTHOPEDICS

Journal of Orthopaedic Surgery and Research Pub Date : 2025-03-25 DOI:10.1186/s13018-025-05721-3

Cheng Li, Ming Chen, Lijun Guo, Dadong Yu, Zhonghai Xu, Bin Chen, Zhijian Xiao

{"title":"Bone marrow mesenchymal stem cell exosomes improve fracture union via remodeling metabolism in nonunion rat model.","authors":"Cheng Li, Ming Chen, Lijun Guo, Dadong Yu, Zhonghai Xu, Bin Chen, Zhijian Xiao","doi":"10.1186/s13018-025-05721-3","DOIUrl":null,"url":null,"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.","PeriodicalId":16629,"journal":{"name":"Journal of Orthopaedic Surgery and Research","volume":"20 1","pages":"308"},"PeriodicalIF":2.8000,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934688/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Orthopaedic Surgery and Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13018-025-05721-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ORTHOPEDICS","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Orthopaedic Surgery and Research ORTHOPEDICS-

CiteScore

4.10

自引率

7.70%

发文量

494

审稿时长

>12 weeks

期刊介绍： Journal of Orthopaedic Surgery and Research is an open access journal that encompasses all aspects of clinical and basic research studies related to musculoskeletal issues. Orthopaedic research is conducted at clinical and basic science levels. With the advancement of new technologies and the increasing expectation and demand from doctors and patients, we are witnessing an enormous growth in clinical orthopaedic research, particularly in the fields of traumatology, spinal surgery, joint replacement, sports medicine, musculoskeletal tumour management, hand microsurgery, foot and ankle surgery, paediatric orthopaedic, and orthopaedic rehabilitation. The involvement of basic science ranges from molecular, cellular, structural and functional perspectives to tissue engineering, gait analysis, automation and robotic surgery. Implant and biomaterial designs are new disciplines that complement clinical applications. JOSR encourages the publication of multidisciplinary research with collaboration amongst clinicians and scientists from different disciplines, which will be the trend in the coming decades.