Evidence map›Paper›PMID 40671164›Full record

ArticleStem cell research & therapy2025

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

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

Abstract read
In one paragraph

Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Zhilong Pi *Guangdong Key Lab of Orthopaedic Technology and Implant Materials, Key Laboratory of Trauma and Tissue Repair of Tropical Area of PLA, Hospital of Orthopaedics, General Hospital of Southern Theater Command of PLA, 111 Liuhua Road, Guangzhou, 510010, Guangdong, China.
You Wu *Guangdong Key Lab of Orthopaedic Technology and Implant Materials, Key Laboratory of Trauma and Tissue Repair of Tropical Area of PLA, Hospital of Orthopaedics, General Hospital of Southern Theater Command of PLA, 111 Liuhua Road, Guangzhou, 510010, Guangdong, China.
Jingyi WuGuangdong Key Lab of Orthopaedic Technology and Implant Materials, Key Laboratory of Trauma and Tissue Repair of Tropical Area of PLA, Hospital of Orthopaedics, General Hospital of Southern Theater Command of PLA, 111 Liuhua Road, Guangzhou, 510010, Guangdong, China.
Tao ZhangGuangdong Key Lab of Orthopaedic Technology and Implant Materials, Key Laboratory of Trauma and Tissue Repair of Tropical Area of PLA, Hospital of Orthopaedics, General Hospital of Southern Theater Command of PLA, 111 Liuhua Road, Guangzhou, 510010, Guangdong, China. gzlupus@126.com.
Pingyue LiGuangdong Key Lab of Orthopaedic Technology and Implant Materials, Key Laboratory of Trauma and Tissue Repair of Tropical Area of PLA, Hospital of Orthopaedics, General Hospital of Southern Theater Command of PLA, 111 Liuhua Road, Guangzhou, 510010, Guangdong, China. lipingyue@smu.edu.cn.
Renkai WangGuangdong Key Lab of Orthopaedic Technology and Implant Materials, Key Laboratory of Trauma and Tissue Repair of Tropical Area of PLA, Hospital of Orthopaedics, General Hospital of Southern Theater Command of PLA, 111 Liuhua Road, Guangzhou, 510010, Guangdong, China. 501214241@qq.com.ORCID http://orcid.org/0000-0002-3942-8739

Funding

Guangzhou Municipal Science and Technology Project 2024A03J0634Guangzhou Municipal Science and Technology Project 2024A03J0690Guangzhou Science, Technology and Innovation Commission 2023A03J0693Natural Science Foundation of Guangdong Province 2022A1515010307Natural Science Foundation of Guangdong Province 2024A1515012050
6 · The paper itself

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.

Indexed as

Activating Transcription Factor 4eIF-2 KinaseExosomesNeovascularization, PhysiologicOsteogenesisAngiogenesisAnimalsEndoplasmic Reticulum StressHumansHuman Umbilical Vein Endothelial CellsMiceOsteoblastsSignal TransductionActivating Transcription Factor 4ATF4 protein, humanEIF2AK3 protein, humaneIF-2 KinaseAngiogenesisCRELD2Endoplasmic reticulum stressEndotheliumExosomeOsteogenesis

Identifiers

PMID40671164
PMCPMC12269303

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.