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

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 diseas...

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Main Authors: Dan Yang, Haitang Wei, Yang Sheng, Tao Peng, Qiang Zhao, Liang Xie, Jun Yang
Format: Article
Language:English
Published: BMC 2024-01-01
Series:Journal of Orthopaedic Surgery and Research
Subjects:
Online Access:https://doi.org/10.1186/s13018-023-04523-9
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author Dan Yang
Haitang Wei
Yang Sheng
Tao Peng
Qiang Zhao
Liang Xie
Jun Yang
author_facet Dan Yang
Haitang Wei
Yang Sheng
Tao Peng
Qiang Zhao
Liang Xie
Jun Yang
author_sort Dan Yang
collection DOAJ
description 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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spelling doaj.art-f774d8b2b0984aed9092dc133dd44ddc2024-01-14T12:30:02ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2024-01-0119111310.1186/s13018-023-04523-9Circ_0006640 transferred by bone marrow-mesenchymal stem cell-exosomes suppresses lipopolysaccharide-induced apoptotic, inflammatory and oxidative injury in spinal cord injuryDan Yang0Haitang Wei1Yang Sheng2Tao Peng3Qiang Zhao4Liang Xie5Jun Yang6Department of Rehabilitation Medicine, Hankou Hospital of WuhanDepartment of Rehabilitation Medicine, Hankou Hospital of WuhanDepartment of Rehabilitation Medicine, Hankou Hospital of WuhanDepartment of Rehabilitation Medicine, Hankou Hospital of WuhanDepartment of Rehabilitation Medicine, Hankou Hospital of WuhanDepartment of Rehabilitation Medicine, Hankou Hospital of WuhanDepartment of Rehabilitation Medicine, Hankou Hospital of WuhanAbstract 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.https://doi.org/10.1186/s13018-023-04523-9Spinal cord injurycirc_0006640miR-382-5pIGF-1LPSExosome
spellingShingle Dan Yang
Haitang Wei
Yang Sheng
Tao Peng
Qiang Zhao
Liang Xie
Jun Yang
Circ_0006640 transferred by bone marrow-mesenchymal stem cell-exosomes suppresses lipopolysaccharide-induced apoptotic, inflammatory and oxidative injury in spinal cord injury
Journal of Orthopaedic Surgery and Research
Spinal cord injury
circ_0006640
miR-382-5p
IGF-1
LPS
Exosome
title Circ_0006640 transferred by bone marrow-mesenchymal stem cell-exosomes suppresses lipopolysaccharide-induced apoptotic, inflammatory and oxidative injury in spinal cord injury
title_full Circ_0006640 transferred by bone marrow-mesenchymal stem cell-exosomes suppresses lipopolysaccharide-induced apoptotic, inflammatory and oxidative injury in spinal cord injury
title_fullStr Circ_0006640 transferred by bone marrow-mesenchymal stem cell-exosomes suppresses lipopolysaccharide-induced apoptotic, inflammatory and oxidative injury in spinal cord injury
title_full_unstemmed Circ_0006640 transferred by bone marrow-mesenchymal stem cell-exosomes suppresses lipopolysaccharide-induced apoptotic, inflammatory and oxidative injury in spinal cord injury
title_short Circ_0006640 transferred by bone marrow-mesenchymal stem cell-exosomes suppresses lipopolysaccharide-induced apoptotic, inflammatory and oxidative injury in spinal cord injury
title_sort circ 0006640 transferred by bone marrow mesenchymal stem cell exosomes suppresses lipopolysaccharide induced apoptotic inflammatory and oxidative injury in spinal cord injury
topic Spinal cord injury
circ_0006640
miR-382-5p
IGF-1
LPS
Exosome
url https://doi.org/10.1186/s13018-023-04523-9
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