MATN3 delivered by exosome from synovial mesenchymal stem cells relieves knee osteoarthritis: Evidence from in vitro and in vivo studies

Long Long; Guoyou Zou; Yi Cheng; Feng Li; Hao Wu; Yixin Shen

doi:10.1016/j.jot.2023.06.003

MATN3 delivered by exosome from synovial mesenchymal stem cells relieves knee osteoarthritis: Evidence from in vitro and in vivo studies

J Orthop Translat. 2023 Aug 11:41:20-32. doi: 10.1016/j.jot.2023.06.003. eCollection 2023 Jul.

Authors

Long Long^{1

2}, Guoyou Zou², Yi Cheng², Feng Li², Hao Wu², Yixin Shen¹

Affiliations

¹ Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu Province, China.
² Department of Orthopedics, The First People's Hospital of Yancheng, Yancheng, 224001, Jiangsu Province, China.

Abstract

Background: Synovial mesenchymal stem cell (SMSC) exerts chondroprotective effects in osteoarthritis (OA) clinical models. However, the regulatory potentials of SMSC-derived exosomes (SMSC-Exo) in OA still need to be discovered, which attracted our attention.

Methods: The destabilization of the medial meniscus surgery was performed on the knee joints of a mouse OA model, followed by injection of SMSC-Exo. In addition, SMSC-Exo was administrated to mouse chondrocytes to observe the functional and molecular alterations.

Results: Both of SMSC-Exo and overexpression of Matrilin-3 (MATN3) alleviated cartilage destruction and suppressed degradation of extracellular matrix (ECM) in the OA rat model. In addition, assays concerning the in vitro OA model induced by IL-1β showed that SMSC-Exo could promote chondrocyte viability and inhibit autophagy defects. Furthermore, SMSC-Exo achieved the chondroprotective effects through the delivery of MATN3/IL-17A, and MATN3 could suppress the activation of PI3K/AKT/mTOR signaling through IL-17A.

Conclusion: SMSC-Exo exerts beneficial therapeutic effects on OA by preventing ECM degradation and autophagy defects by delivering MATN3/IL-17A.

The translational potential of this article: The translational potential of this study is not only limited to the treatment of knee osteoarthritis but also provides new insights for the treatment of other joint diseases by exploring the mechanism of MATN3. In addition, SMSCExo, as a novel drug carrier, has great potential for treating and diagnosing other diseases. With further research, these findings will provide new directions for developing personalized and innovative treatment options.

Keywords: Exosomes; IL-17A; Knee osteoarthritis; MATN3; PI3K/AKT/mTOR signaling pathway; Synovial mesenchymal stem cells.