Exosomal miR-423-5p Derived from Mineralized Osteoblasts Promotes Angiogenesis of Endothelial Cells by Targeting CXCL10

Feng Long; Hailong Li; Xujun Chen; Yiqun He; Youhai Dong

doi:10.31083/j.fbl2908278

Frontiers in Bioscience-Landmark (Aug 2024)

Exosomal miR-423-5p Derived from Mineralized Osteoblasts Promotes Angiogenesis of Endothelial Cells by Targeting CXCL10

Feng Long,
Hailong Li,
Xujun Chen,
Yiqun He,
Youhai Dong

Affiliations

Feng Long: Department of Orthopedics, Shanghai Fifth People’s Hospital, Fudan University, 200240 Shanghai, China
Hailong Li: Department of Orthopedics, Shanghai Fifth People’s Hospital, Fudan University, 200240 Shanghai, China
Xujun Chen: Department of Orthopedics, Shanghai Fifth People’s Hospital, Fudan University, 200240 Shanghai, China
Yiqun He: Department of Orthopedics, Shanghai Fifth People’s Hospital, Fudan University, 200240 Shanghai, China
Youhai Dong: Department of Orthopedics, Shanghai Fifth People’s Hospital, Fudan University, 200240 Shanghai, China

DOI: https://doi.org/10.31083/j.fbl2908278
Journal volume & issue: Vol. 29, no. 8
p. 278

Abstract

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Background: Bone tissue engineering offers a new approach for the treatment of bone defects, with angiogenesis being critical to the survival and development of tissue-engineered bone. Mineralized osteoblasts (MOBs) have been reported to promote vascular formation by endothelial cells (ECs) through the secretion of exosomes containing a variety of angiogenic factors. The aim of the present study was to investigate the effect of miR-423-5p contained within exosomes derived from MOBs (MOB-Exos) on EC angiogenesis. Methods: The Cell Counting Kit-8 (CCK-8), scratch wound healing, Transwell migration, and tube formation assays were conducted to assess the in vitro effects of MOB-Exos on EC proliferation, migration, and tubule-forming capabilities. The miR-423-5p level in MOB-Exos was quantified using quantitative polymerase chain reaction (qPCR). Co-culture experiments were used to study the exosomal transport of miR-423-5p and its angiogenic effects. High-throughput sequencing was used to identify differentially expressed genes, and a dual luciferase reporter assay to determine whether CXCL10 was a direct target gene for miR-423-5p. Furthermore, the in vivo effect of MOB-Exos-derived miR-423-5p on angiogenesis was evaluated using a subcutaneous xenograft model. Results: MOB-Exos significantly promoted the in vitro proliferation, migration, and tubule formation of ECs. A high level of miR-423-5p was found in MOB-Exos and promoted the angiogenesis of ECs. The CXCL10 gene was significantly downregulated in ECs upon miR-423-5p mimic transfection. Dual luciferase reporter assay confirmed the direct binding of miR-423-5p to the CXCL10 gene. miR-423-5p derived from MOB-Exos upregulated expression of the vascular markers CD31 and vascular endothelial growth factor (VEGF) in vivo, thus underscoring its angiogenic potential. Conclusion: This study found that miR-423-5p derived from MOB-Exos could potentially enhance EC angiogenesis via the regulation of CXCL10. Therefore, exosomes are promising therapeutic candidates for clinical bone defects.

Published in Frontiers in Bioscience-Landmark

ISSN: 2768-6701 (Print); 2768-6698 (Online)
Publisher: IMR Press
Country of publisher: Singapore
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry; Science: Biology (General)
Website: https://www.imrpress.com/journal/FBL

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