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骨髓间充质干细胞外泌体通过重塑骨不连大鼠模型的代谢来促进骨折愈合。

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

作者信息

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

机构信息

Hangzhou Fuyang Hospital of TCM Orthopedics and Traumatology, Hangzhou, Zhejiang, 311400, China.

出版信息

J Orthop Surg Res. 2025 Mar 25;20(1):308. doi: 10.1186/s13018-025-05721-3.

DOI:10.1186/s13018-025-05721-3
PMID:40128748
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11934688/
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.

摘要

背景

骨折不愈合是骨科临床治疗和预后中一个尚未解决的主要问题。骨髓间充质干细胞（BMSC）外泌体已被证明参与多种疾病中组织和骨再生的介导过程。然而，BMSC外泌体在骨折不愈合中的作用尚不清楚。

方法

将BMSC外泌体注入大鼠骨折不愈合模型中，通过显微CT检测骨折愈合部位，并通过液相色谱-串联质谱法（LC-MS/MS）分析血清代谢产物。

结果

结果表明，外泌体可以从无外泌体培养基中培养的大鼠BMSC中成功分离出来。与模型组相比，外泌体处理的大鼠骨折部位愈合明显。与PBS组相比，BMSC-外泌体组有158种上调的差异丰度代谢产物（DAM）和79种下调的DAM。这些DAM富集在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”中。HIF-1信号通路中的DAM-PE是促进骨折愈合的主要代谢产物。

结论

我们的研究揭示了BMSC-外泌体通过代谢重编程改善骨折愈合过程的机制，并为骨折不愈合的治疗提供了参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffdf/11934688/08783c9987df/13018_2025_5721_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffdf/11934688/b22a8d357c70/13018_2025_5721_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffdf/11934688/34e72e5e6cb7/13018_2025_5721_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffdf/11934688/6f595c53d692/13018_2025_5721_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffdf/11934688/84a7d2043161/13018_2025_5721_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffdf/11934688/08783c9987df/13018_2025_5721_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffdf/11934688/b22a8d357c70/13018_2025_5721_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffdf/11934688/34e72e5e6cb7/13018_2025_5721_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffdf/11934688/6f595c53d692/13018_2025_5721_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffdf/11934688/84a7d2043161/13018_2025_5721_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffdf/11934688/08783c9987df/13018_2025_5721_Fig5_HTML.jpg

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本文引用的文献

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J Orthop Surg Res. 2024 Dec 18;19(1):828. doi: 10.1186/s13018-024-05351-1.
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Functional mechanism and clinical implications of mir-1271-5p in pilon fracture healing processes.miR-1271-5p 在 Pilon 骨折愈合过程中的功能机制及临床意义
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lncRNA CASC11 regulates the progress of delayed fracture healing via sponging miR-150-3p.长链非编码 RNA CASC11 通过海绵吸附 miR-150-3p 调控延迟骨折愈合的进程。
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The predictive value of stress-induced hyperglycemia parameters for delayed healing after tibial fracture post-surgery.应激性高血糖参数对胫骨骨折术后延迟愈合的预测价值。
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Functional mechanism and clinical implications of LINC00339 in delayed fracture healing.LINC00339 在延迟性骨折愈合中的功能机制及临床意义。
J Orthop Surg Res. 2024 Aug 27;19(1):511. doi: 10.1186/s13018-024-04998-0.
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Pharmacological agents for bone fracture healing: talking points from recent clinical trials.骨折愈合的药理学药物：近期临床试验的讨论要点。
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