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Exosomal miR-9-5p secreted by bone marrow–derived mesenchymal stem cells alleviates osteoarthritis by inhibiting syndecan-1

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Abstract

Mesenchymal stem cells (MSCs) have been demonstrated to serve as targets for the treatment of osteoarthritis (OA) and exosomes derived from MSCs also display chondroprotective effects. This study aims to investigate the regulatory role of exosomal microRNA-9-5p (miR-9-5p) secreted by bone marrow–derived MSCs (BM-MSCs) on OA in a rat model induced by anterior cruciate ligament/medial collateral ligament transection. Luciferase reporter assay was conducted to verify the putative miR-9-5p binding sites to 3′UTR of syndecan-1 (SDC1). Additionally, an intra-articular injection of miR-9-5p carried by BM-MSC–derived exosomes or liposomes into rats with OA-like damage was performed to ascertain the role of exosomal miR-9-5p and a gain-of-function study of SDC1 was carried out to explore the potential mechanism in relation to SDC1. Subsequently, the expression of SDC1 was determined and the levels of inflammatory factors (IL-1, IL-6, TNF-α and CRP) and oxidative stress injury indicators (NO, MDA, iNOS, COX2 and SOD), the contents of AKP as well as the levels of OA-related factors (MMP-13, COMP and OCN) were measured. Injection of miR-9-5p-contained exosomes resulted in an alleviation of inflammation and OA-like damage, which was evidenced by downregulated levels of inflammatory factors, reduced oxidative stress injury and decreased OCN, MMP-13, COMP and AKP levels. As a target gene of miR-9-5p, the upregulation of SDC1 led to aggravation of inflammation and OA-like damage, which is opposite to exosomal miR-9-5p. To conclude, these findings suggest the anti-inflammatory and chondroprotective effects of BM-MSC–derived exosomal miR-9-5p on OA via regulation of SDC1.

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Acknowledgments

We would like to give our sincere appreciation to the reviewers for their helpful comments on this article.

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Authors and Affiliations

  1. Department of Orthopaedics, First Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, People’s Republic of China

    Zhe Jin & Jiaan Ren

  2. Department of Orthopaedics, Dashiqiao Central Hospital, Shenyang, 115100, People’s Republic of China

    Shanlun Qi

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  1. Zhe Jin
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  2. Jiaan Ren
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Correspondence to Zhe Jin.

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The animal experiments in our study were conducted strictly in accordance with the guidelines of National Institutes of Health (NIH) for animal care and use, with an approval from the Animal Ethics Committee of First Hospital of China Medical University.

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Jin, Z., Ren, J. & Qi, S. Exosomal miR-9-5p secreted by bone marrow–derived mesenchymal stem cells alleviates osteoarthritis by inhibiting syndecan-1. Cell Tissue Res 381, 99–114 (2020). https://doi.org/10.1007/s00441-020-03193-x

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  • DOI: https://doi.org/10.1007/s00441-020-03193-x

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