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源自骨髓间充质干细胞的外泌体在体外模型中可诱导骨髓炎中的细胞增殖和成骨分化,并调节炎症状态。

Exosomes derived from bone marrow mesenchymal stem cells induce the proliferation and osteogenic differentiation and regulate the inflammatory state in osteomyelitis in vitro model.

作者信息

Liang Wei, Li Yangui, Ji Yihua, Kang Renjie, Zhang Kaixi, Su Xueyuan, Li Jiangbo, Ji Mingming, Wu Taiyong, Cao Xinjie, Chen Jianrui, Huo Jianzhong

机构信息

Department of Orthopaedics, Taiyuan Hospital of Peking University First Hospital (Taiyuan Central Hospital), No. 1, East Sandao Lane, Jiefang Road, Taiyuan, 030000, Shanxi Province, China.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Feb;398(2):1695-1705. doi: 10.1007/s00210-024-03357-4. Epub 2024 Aug 21.

DOI:10.1007/s00210-024-03357-4
PMID:39168906
Abstract

Chronic osteomyelitis is a chronic bone infection characterized by progressive osteonecrosis and dead bone formation, which is closely related to persistent infection and chronic inflammation. Exosomes derived from bone marrow-derived mesenchymal stem cells (BMSC) play an important role in bone tissue regeneration and the modulation of inflammatory processes. However, their role and mechanism of action in osteomyelitis have not been reported so far. This paper explores the potential effect of BMSC-derived exosomes on osteomyelitis in vitro model with the aim of providing a theoretical basis for the treatment of osteomyelitis in the future. In this study, exosomes were isolated and extracted from BMSCs and identified. MC3T3-E1 cells were treated with Staphylococcal protein A (SPA) to establish an in vitro model of osteomyelitis. Next, the effects of BMSC-derived exosomes on cell proliferation, apoptosis, angiogenesis, and autophagy in MC3T3-E1 cells treated with SPA were evaluated. Results showed that the proliferation ability of MC3T3-E1 cells increased after co-culture with BMSC-derived exosomes. Moreover, exosomes induced autophagy and osteogenic differentiation in MC3T3-E1 cells. The mRNA and protein levels of factors related to proliferation, differentiation, apoptosis, autophagy, and angiogenesis including β-Catenin, Runx2, Bcl-2, VEGFA, and Beclin-1 upregulated in SPA-treated MC3T3-E1 cells, whereas the levels of inflammatory cytokines including TNF-α, IL-1β, and IL-6 decreased in the supernatant. The results showed that exosomes derived from BMSCs may participate in the attenuation of osteomyelitis by inducing proliferation and osteogenic differentiation and regulating the inflammatory state in bone cells.

摘要

慢性骨髓炎是一种慢性骨感染,其特征为进行性骨坏死和死骨形成,与持续感染和慢性炎症密切相关。源自骨髓间充质干细胞(BMSC)的外泌体在骨组织再生和炎症过程调节中发挥重要作用。然而,其在骨髓炎中的作用及作用机制迄今尚未见报道。本文旨在探讨BMSC来源的外泌体在体外骨髓炎模型中的潜在作用,为未来骨髓炎的治疗提供理论依据。在本研究中,从BMSCs中分离提取并鉴定外泌体。用葡萄球菌蛋白A(SPA)处理MC3T3-E1细胞以建立骨髓炎体外模型。接下来,评估BMSC来源的外泌体对经SPA处理的MC3T3-E1细胞的细胞增殖、凋亡、血管生成和自噬的影响。结果显示,与BMSC来源的外泌体共培养后,MC3T3-E1细胞的增殖能力增强。此外,外泌体诱导MC3T3-E1细胞发生自噬和成骨分化。在经SPA处理的MC3T3-E1细胞中,与增殖、分化、凋亡、自噬和血管生成相关的因子β-连环蛋白、Runx2、Bcl-2、VEGFA和Beclin-1的mRNA和蛋白水平上调,而上清液中包括TNF-α、IL-1β和IL-6在内的炎性细胞因子水平降低。结果表明,BMSCs来源的外泌体可能通过诱导增殖和成骨分化以及调节骨细胞的炎症状态参与骨髓炎的减轻过程。

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本文引用的文献

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BMSC-Derived Exosomal CircHIPK3 Promotes Osteogenic Differentiation of MC3T3-E1 Cells via Mitophagy.骨髓间充质干细胞衍生的外泌体环状 RNA HIPK3 通过促进自噬促进 MC3T3-E1 细胞的成骨分化。
Int J Mol Sci. 2023 Feb 1;24(3):2785. doi: 10.3390/ijms24032785.
2
Inhibition of autophagy potentiates the cytotoxicity of the irreversible FGFR1-4 inhibitor FIIN-2 on lung adenocarcinoma.自噬抑制增强不可逆 FGFR1-4 抑制剂 FIIN-2 对肺腺癌的细胞毒性。
Cell Death Dis. 2022 Aug 30;13(8):750. doi: 10.1038/s41419-022-05201-0.
3
Exosome-delivered BMP-2 and polyaspartic acid promotes tendon bone healing in rotator cuff tear via Smad/RUNX2 signaling pathway.
细胞死亡机制及其在间充质干细胞修复炎症性肠病中的应用
Front Immunol. 2025 Jun 4;16:1597462. doi: 10.3389/fimmu.2025.1597462. eCollection 2025.
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Application of autophagy in mesenchymal stem cells.自噬在间充质干细胞中的应用。
World J Stem Cells. 2024 Dec 26;16(12):990-1001. doi: 10.4252/wjsc.v16.i12.990.
外泌体递送的骨形态发生蛋白 2 和聚天冬氨酸通过 Smad/RUNX2 信号通路促进肩袖撕裂的腱骨愈合。
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Skeletal infections: microbial pathogenesis, immunity and clinical management.骨骼感染:微生物发病机制、免疫与临床管理。
Nat Rev Microbiol. 2022 Jul;20(7):385-400. doi: 10.1038/s41579-022-00686-0. Epub 2022 Feb 15.
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Acta Biomater. 2022 Jan 1;137:305-315. doi: 10.1016/j.actbio.2021.10.026. Epub 2021 Oct 20.
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J Cell Mol Med. 2021 Nov;25(22):10454-10465. doi: 10.1111/jcmm.16974. Epub 2021 Oct 9.
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miR-27a-5p-Abundant Small Extracellular Vesicles Derived From Epimedium-Preconditioned Bone Mesenchymal Stem Cells Stimulate Osteogenesis by Targeting Atg4B-Mediated Autophagy.淫羊藿预处理的骨髓间充质干细胞来源的富含miR-27a-5p的小细胞外囊泡通过靶向Atg4B介导的自噬刺激成骨作用。
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