Long Long, Zou Guoyou, Cheng Yi, Li Feng, Wu Hao, Shen Yixin
Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu Province, China.
Department of Orthopedics, The First People's Hospital of Yancheng, Yancheng, 224001, Jiangsu Province, China.
J Orthop Translat. 2023 Aug 11;41:20-32. doi: 10.1016/j.jot.2023.06.003. eCollection 2023 Jul.
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.
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.
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 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.
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 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.
滑膜间充质干细胞（SMSC）在骨关节炎（OA）临床模型中发挥软骨保护作用。然而，SMSC衍生的外泌体（SMSC-Exo）在OA中的调节潜力仍有待发现，这引起了我们的关注。
对小鼠OA模型的膝关节进行内侧半月板手术使其不稳定，随后注射SMSC-Exo。此外，将SMSC-Exo应用于小鼠软骨细胞以观察功能和分子变化。
SMSC-Exo和基质金属蛋白酶3（MATN3）的过表达均减轻了OA大鼠模型中的软骨破坏并抑制了细胞外基质（ECM）的降解。此外，关于IL-1β诱导的OA模型的实验表明，SMSC-Exo可以促进软骨细胞活力并抑制自噬缺陷。此外，SMSC-Exo通过递送MATN3/IL-17A实现软骨保护作用，并且MATN3可以通过IL-17A抑制PI3K/AKT/mTOR信号通路的激活。
SMSC-Exo通过递送MATN3/IL-17A预防ECM降解和自噬缺陷，从而对OA发挥有益的治疗作用。
本研究的转化潜力不仅限于膝关节骨关节炎的治疗，还通过探索MATN3的机制为其他关节疾病的治疗提供了新的见解。此外，SMSCExo作为一种新型药物载体，在治疗和诊断其他疾病方面具有巨大潜力。随着进一步的研究，这些发现将为开发个性化和创新性治疗方案提供新的方向。
