Tailored apoptotic vesicles promote bone regeneration by stepping on osteoinductive accelerator via ITGA10-AKT signaling activation

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today Pub Date : 2025-10-06 DOI:10.1016/j.nantod.2025.102912

Yuhe Jiang , Zeying Wang , Ruiyi Guo , Yike Liao , Hao Qiu , Yunsong Liu , Ping Zhang , Yuan Zhu , Wenyue Li , Xiao Zhang , Yongsheng Zhou

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引用次数: 0

Abstract

Apoptotic vesicles (apoVs) have shown good potential in treating bone disease including osteoporosis. However, the efficient production of highly energetic apoVs is one of the critical limitations for their clinical applications. In this study, we contributed to reconstructing a gradual senescence process in mesenchymal stem cell (MSC)-derived apoVs. Our findings displayed that their essential properties remained consistent throughout replicative aging and individual’s aging. Nevertheless, their protein composition and biological functions were significantly altered by the age of donor. Through proteomic assay, we identified integrin α 10 (ITGA10) as a highly efficient apoV osteoinductivity accelerator in both humans and mice, and have targeted it for apoV customization. On this basis, we demonstrated accelerator-based approaches to prepare amounts of ITGA10-enriched apoVs by magnetic-activated sorting and sonic loading. These engineered apoVs proved effective in ameliorating osteoprotic bone loss. Their osteoinductivity was attributed to the activation of downstream AKT signaling in recipient MSCs by the high content of ITGA10. In summary, we have laid the groundwork for customizing apoVs through an accelerator-based strategy, aiming to obtain superior therapeutic effectors in the field of bone regenerative biomedicine.

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定制的凋亡囊泡通过ITGA10-AKT信号激活，通过踩骨诱导加速器促进骨再生

凋亡囊泡（apoVs）在治疗骨质疏松等骨病方面显示出良好的潜力。然而，高效生产高能载脂蛋白是其临床应用的关键限制之一。在这项研究中，我们重建了间充质干细胞（MSC）衍生的apoVs的逐渐衰老过程。我们的研究结果表明，它们的基本特性在复制衰老和个体衰老过程中保持一致。然而，它们的蛋白质组成和生物学功能随着供体年龄的变化而显著改变。通过蛋白质组学分析，我们发现整合素α 10 （ITGA10）在人类和小鼠中都是一种高效的apoV骨诱导促进剂，并针对apoV定制。在此基础上，我们展示了基于加速器的方法，通过磁激活分选和声波加载制备大量富含itga10的apov。这些工程化的apov被证明在改善骨质流失方面是有效的。它们的成骨性归因于高含量的ITGA10激活了受体MSCs中的下游AKT信号。综上所述，我们已经通过基于加速器的策略为定制apov奠定了基础，旨在骨再生生物医学领域获得卓越的治疗效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nano Today 工程技术-材料科学：综合

CiteScore

21.50

自引率

3.40%

发文量

305

审稿时长

40 days

期刊介绍： Nano Today is a journal dedicated to publishing influential and innovative work in the field of nanoscience and technology. It covers a wide range of subject areas including biomaterials, materials chemistry, materials science, chemistry, bioengineering, biochemistry, genetics and molecular biology, engineering, and nanotechnology. The journal considers articles that inform readers about the latest research, breakthroughs, and topical issues in these fields. It provides comprehensive coverage through a mixture of peer-reviewed articles, research news, and information on key developments. Nano Today is abstracted and indexed in Science Citation Index, Ei Compendex, Embase, Scopus, and INSPEC.