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Synovial mesenchymal stem cell-derived exosomal microRNA-320c facilitates cartilage damage repair by targeting ADAM19-dependent Wnt signalling in osteoarthritis rats

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Abstract

Objective

Our previous study revealed that synovial mesenchymal stem cell (SMSC)-derived exosomal microRNA-302c enhanced chondrogenesis by targeting a disintegrin and metalloproteinase 19 (ADAM19) in vitro. This study aimed to validate the potential of SMSC-derived exosomal microRNA-302c for the treatment of osteoarthritis in vivo.

Methods

After 4 weeks of destabilization of the medial meniscus surgery (DMM) to establish an osteoarthritis model, the rats received weekly articular cavity injection of SMSCs with or without GW4869 treatment (exosome inhibitor) or exosomes from SMSCs with or without microRNA-320c overexpression for another 4 weeks.

Results

SMSCs and SMSC-derived exosomes reduced the Osteoarthritis Research Society International (OARSI) score, improved cartilage damage repair, suppressed cartilage inflammation, suppressed extracellular matrix (ECM) degradation, and inhibited chondrocyte apoptosis in DMM rats. However, these effects were largely hampered in rats that were injected with GW4869-treated SMSCs. Moreover, exosomes from microRNA-320c-overexpressing SMSCs exerted a better effect than exosomes from negative control SMSCs on decreasing the OARSI score, enhancing cartilage damage repair, suppressing cartilage inflammation, and inhibiting ECM degradation and chondrocyte apoptosis. Mechanistically, exosomes from microRNA-320c-overexpressing SMSCs reduced the levels of ADAM19, as well as β-catenin and MYC, which are two critical proteins in Wnt signalling.

Conclusion

SMSC-derived exosomal microRNA-320c suppresses ECM degradation and chondrocyte apoptosis to facilitate cartilage damage repair in osteoarthritis rats by targeting ADAM19-dependent Wnt signalling.

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Data availability

The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by the National Natural Science Foundation of China (No. 81901583).

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Author notes

  1. Ruina Kong, Ju Zhang and Lianmei Ji have contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology and Immunology, The First Affiliated Hospital of Naval Medical University, No. 168 Changhai Road, Shanghai, 200433, China

    Ruina Kong, Ju Zhang, Lianmei Ji, Yiyi Yu, Jie Gao & Dongbao Zhao

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  1. Ruina Kong
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  2. Ju Zhang
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  3. Lianmei Ji
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  4. Yiyi Yu
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  5. Jie Gao
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Corresponding authors

Correspondence to Jie Gao or Dongbao Zhao.

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Conflict of interest

The authors have no relevant financial or nonfinancial interests to disclose.

Ethical approval

This study was approved by the Animal Care and Use Committee (reference number: CHEC2020-105, approval date: 2020.9.27). All animal experiments were performed in accordance with the animal guidelines of the National Institutes of Health.

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10787_2023_1142_MOESM1_ESM.tif

Supplementary Figure 1. Effect of different doses of SMSC-derived exosomes on cartilage damage repair. SOFA and HE staining of joint samples in the groups (A). Comparison of OARSI scores among the groups (B) (TIF 17314 KB)

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Kong, R., Zhang, J., Ji, L. et al. Synovial mesenchymal stem cell-derived exosomal microRNA-320c facilitates cartilage damage repair by targeting ADAM19-dependent Wnt signalling in osteoarthritis rats. Inflammopharmacol 31, 915–926 (2023). https://doi.org/10.1007/s10787-023-01142-y

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