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

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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.

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骨髓间充质干细胞外泌体通过重塑代谢促进骨不连大鼠骨折愈合。

背景：骨折不愈合是骨科临床治疗和预后中尚未解决的主要问题。骨髓间充质干细胞（BMSC）外泌体已被证明在多种疾病中参与介导组织和骨再生。然而，BMSC外泌体在骨折不愈合中的作用尚不清楚。方法：将BMSC外泌体注射到骨折不愈合大鼠模型中，采用micro-CT检测骨折愈合部位，LC-MS/MS分析血清代谢物。结果：在无外泌体培养基中培养的大鼠骨髓间充质干细胞可成功分离到外泌体。与模型组比较，外泌体治疗大鼠骨折部位愈合明显。与PBS组相比，BMSC-exo组有158个差异丰度代谢物上调，79个差异丰度代谢物下调。dam富集与细胞增殖和分化功能相关的“Th1和Th2细胞分化”、“ErbB信号通路”、“PPAR信号通路”和“HIF-1信号通路”。HIF-1信号通路中的DAMs-PE是促进骨折愈合的主要代谢物。结论：我们的研究揭示了骨髓间质干细胞外泌体通过代谢重编程促进骨折愈合的机制，为骨折不愈合的治疗提供参考。

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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.