Endothelial cell-secreted bone targeting exosomes promote angiogenesis coupling with osteogenesis via the PERK-ATF4-CRELD2 pathway.

IF 7.1 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cell Research & Therapy Pub Date : 2025-07-16 DOI:10.1186/s13287-025-04449-5

Zhilong Pi, You Wu, Jingyi Wu, Tao Zhang, Pingyue Li, Renkai Wang

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引用次数: 0

Abstract

The role of endoplasmic reticulum (ER) stress in bone metabolism and the management of associated diseases has garnered significant interest. However, its role in regulating bone homeostasis and skeletal development remains largely unclear. Osteoblast development and bone formation are enhanced by a particular subtype of CD31hi endomucinhi (CD31hiEMCNhi) endothelium. However, it is still unclear how endothelial exosomes contribute to the production of CD31hiEMCNhi endothelium and bone formation. This research revealed that human umbilical vein endothelial cells (HUVECs)-exosomes (Exos) enhanced the formation of osteoblast and angiogenic effects in vitro. Furthermore, in mice treated with HUVECs-Exos, osteoblast production, and CD31hiEmcnhi vessels were significantly increased. The mechanism by which HUVECs-Exos CRELD2 improved angiogenesis coupling with osteogenesis involved triggering the PERK-ATF4-CRELD2 pathway's ER stress. As a result, HUVECs-Exos CRELD2 may be used as a potential bone metabolic disease nanodrug.

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内皮细胞分泌骨靶向外泌体通过PERK-ATF4-CRELD2途径促进血管生成与成骨耦合。

内质网（ER）应激在骨代谢和相关疾病管理中的作用已经引起了人们的极大兴趣。然而，其在调节骨稳态和骨骼发育中的作用仍不清楚。一种特殊亚型的CD31hiEMCNhi内皮细胞可促进成骨细胞的发育和骨形成。然而，内皮外泌体如何促进CD31hiEMCNhi内皮细胞的生成和骨形成尚不清楚。本研究揭示了人脐静脉内皮细胞(HUVECs)-外泌体（Exos）在体外促进成骨细胞的形成和血管生成的作用。此外，在HUVECs-Exos处理的小鼠中，成骨细胞的产生和CD31hiEmcnhi血管显著增加。HUVECs-Exos CRELD2促进血管生成与成骨耦合的机制涉及触发PERK-ATF4-CRELD2通路的内质网应激。因此，HUVECs-Exos CRELD2可能被用作潜在的骨代谢性疾病纳米药物。

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

Stem Cell Research & Therapy CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

13.20

自引率

8.00%

发文量

525

审稿时长

1 months

期刊介绍： Stem Cell Research & Therapy serves as a leading platform for translational research in stem cell therapies. This international, peer-reviewed journal publishes high-quality open-access research articles, with a focus on basic, translational, and clinical research in stem cell therapeutics and regenerative therapies. Coverage includes animal models and clinical trials. Additionally, the journal offers reviews, viewpoints, commentaries, and reports.