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Journal of Orthopaedic Surgery and Research
Published in: Journal of Orthopaedic Surgery and Research 1/2024

Open Access 01-12-2024 | Research article

Circ_0006640 transferred by bone marrow-mesenchymal stem cell-exosomes suppresses lipopolysaccharide-induced apoptotic, inflammatory and oxidative injury in spinal cord injury

Authors: Dan Yang, Haitang Wei, Yang Sheng, Tao Peng, Qiang Zhao, Liang Xie, Jun Yang

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2024

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Abstract

Background

Emerging proofs have shown that differentially expressed circular RNAs (circRNAs) are closely associated with the pathophysiological process of spinal cord injury (SCI). Mesenchymal stem cell (MSC)-exosomes have been demonstrated to possess favorable therapeutic effects in diseases. Herein, this work aimed to investigate the action of circ_0006640 transferred by MSC-exosomes functional recovery after SCI.

Methods

SCI animal models were established by spinal cord contusion surgery in mice and lipopolysaccharide (LPS)-stimulated mouse microglial cell line BV2. Levels of genes and proteins were detected by qRT-PCR and Western blot. Properties of BV2 cells were characterized using CCK-8 assay, flow cytometry and ELISA analysis. The oxidative stress was evaluated. Dual-luciferase reporter assay was used for verifying the binding between miR-382-5p and circ_0006640 or IGF-1 (Insulin-like Growth Factor 1). Exosome separation was conducted by using the commercial kit.

Results

Circ_0006640 expression was lower in SCI mice and LPS-induced microglial cells. Circ_0006640 overexpression protected microglial cells from LPS-induced apoptotic, inflammatory and oxidative injury. Mechanistically, circ_0006640 directly sponged miR-382-5p, which targeted IGF-1. MiR-382-5p was increased, while IGF-1 was decreased in SCI mice and LPS-induced microglial cells. Knockdown of miR-382-5p suppressed apoptosis, inflammation and oxidative stress in LPS-induced microglial cells, which were reversed by IGF-1 deficiency. Moreover, miR-382-5p up-regulation abolished the protective functions of circ_0006640 in LPS-induced microglial cells. Additionally, circ_0006640 was packaged into MSC-exosomes and could be transferred by exosomes. Exosomal circ_0006640 also had protective effects on microglial cells via miR-382-5p/IGF-1 axis.

Conclusion

Circ_0006640 transferred by BMSC-exosomes suppressed LPS-induced apoptotic, inflammatory and oxidative injury via miR-382-5p/IGF-1 axis, indicating a new insight into the clinical application of exosomal circRNA-based therapeutic in the function recovery after SCI.
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Metadata
Title
Circ_0006640 transferred by bone marrow-mesenchymal stem cell-exosomes suppresses lipopolysaccharide-induced apoptotic, inflammatory and oxidative injury in spinal cord injury
Authors
Dan Yang
Haitang Wei
Yang Sheng
Tao Peng
Qiang Zhao
Liang Xie
Jun Yang
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2024
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/s13018-023-04523-9

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