Golgi-restored vesicular replenishment retards bone aging and empowers aging bone regeneration

IF 15 1区医学 Q1 CELL & TISSUE ENGINEERING Bone Research Pub Date : 2025-02-08 DOI:10.1038/s41413-024-00386-w

Peisheng Liu, Hao Guo, Xiaoyao Huang, Anqi Liu, Ting Zhu, Chenxi Zheng, Fei Fu, Kaichao Zhang, Shijie Li, Xinyan Luo, Jiongyi Tian, Yan Jin, Kun Xuan, Bingdong Sui

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Abstract

Healthy aging is a common goal for humanity and society, and one key to achieving it is the rejuvenation of senescent resident stem cells and empowerment of aging organ regeneration. However, the mechanistic understandings of stem cell senescence and the potential strategies to counteract it remain elusive. Here, we reveal that the aging bone microenvironment impairs the Golgi apparatus thus diminishing mesenchymal stem cell (MSC) function and regeneration. Interestingly, replenishment of cell aggregates-derived extracellular vesicles (CA-EVs) rescues Golgi dysfunction and empowers senescent MSCs through the Golgi regulatory protein Syntaxin 5. Importantly, in vivo administration of CA-EVs significantly enhanced the bone defect repair rate and improved bone mass in aging mice, suggesting their therapeutic value for treating age-related osteoporosis and promoting bone regeneration. Collectively, our findings provide insights into Golgi regulation in stem cell senescence and bone aging, which further highlight CA-EVs as a potential rejuvenative approach for aging bone regeneration.

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高尔基恢复囊泡补充可延缓骨质老化并促进老化骨再生

健康老龄化是人类和社会的共同目标，实现这一目标的关键之一是衰老常驻干细胞的再生和衰老器官的再生能力。然而，对干细胞衰老的机制理解和对抗它的潜在策略仍然难以捉摸。在这里，我们揭示了老化的骨微环境损害高尔基体，从而减少间充质干细胞（MSC）的功能和再生。有趣的是，细胞聚集源性细胞外囊泡（ca - ev）的补充可通过高尔基调节蛋白Syntaxin 5修复高尔基体功能障碍并增强衰老的MSCs。重要的是，体内给药ca - ev显著提高了衰老小鼠的骨缺损修复率，改善了骨量，提示其在治疗老年性骨质疏松症和促进骨再生方面的治疗价值。总的来说，我们的研究结果为高尔基体在干细胞衰老和骨老化中的调节提供了见解，进一步强调了ca - ev作为衰老骨再生的潜在恢复方法。

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来源期刊

Bone Research CELL & TISSUE ENGINEERING-

CiteScore

20.00

自引率

4.70%

发文量

289

审稿时长

20 weeks

期刊介绍： Established in 2013, Bone Research is a newly-founded English-language periodical that centers on the basic and clinical facets of bone biology, pathophysiology, and regeneration. It is dedicated to championing key findings emerging from both basic investigations and clinical research concerning bone-related topics. The journal's objective is to globally disseminate research in bone-related physiology, pathology, diseases, and treatment, contributing to the advancement of knowledge in this field.