Synovial mesenchymal stem cells (SMSCs) have the potential to attenuate osteoarthritis (OA)-induced injury. The role and mechanism of SMSC-derived exosomes (SMSC-Exos), pivotal paracrine factors of stem cells, in OA-associated injury remain unclear. We aimed to confirm the effect of SMSC-Exos with specific modifications on OA-induced damage and to investigate the potential molecular mechanisms. Exosomes derived from miR-155-5p–overexpressing SMSCs (SMSC-155-5p-Exos) and SMSCs (SMSC-Exos) were isolated and characterized. CCK-8, Transwell, and Western blot analyses were used to detect proliferation, migration, extracellular matrix (ECM) secretion, and apoptosis of osteoarthritic chondrocytes. The therapeutic effect of exosomes in a mouse model of OA was examined using immunohistochemical staining and OARSI scores. SPSS 17.0 and GraphPad software were used for all statistical analyses in this study. The SMSC-Exos enhanced the proliferation and migration and inhibited the apoptosis of osteoarthritic chondrocytes but had no effect on ECM secretion. The miR-155-5p–overexpressing exosomes showed common characteristics of exosomes in vitro and further promoted ECM secretion by targeting Runx2. Thus, the SMSC-155-5p-Exos promoted proliferation and migration, suppressed apoptosis and enhanced ECM secretion of osteoarthritic chondrocytes, and effectively prevented OA in a mouse model. In addition, overexpression of Runx2 partially reversed the effect of the SMSC-155-5p-Exos on osteoarthritic chondrocytes. Given the insufficient effect of the SMSC-Exos on the ECM secretion of osteoarthritic chondrocytes, we modified the SMSM-Exos and demonstrated that the SMSC-155-5p-Exos could prevent OA. Exosomes derived from modified SMSCs may be a new treatment strategy to prevent OA.

滑膜间充质干细胞（SMSC）具有减轻骨关节炎（OA）引起的损伤的潜力。 SMSC 衍生的外泌体 (SMSC-Exos)（干细胞的关键旁分泌因子）在 OA 相关损伤中的作用和机制尚不清楚。我们的目的是确认经过特定修饰的 SMSC-Exos 对 OA 引起的损伤的影响，并研究潜在的分子机制。分离并表征了源自 miR-155-5p 过表达 SMSC (SMSC-155-5p-Exos) 和 SMSC (SMSC-Exos) 的外泌体。 CCK-8、Transwell 和 Western blot 分析用于检测骨关节炎软骨细胞的增殖、迁移、细胞外基质 (ECM) 分泌和凋亡。使用免疫组织化学染色和 OARSI 评分检查外泌体在 OA 小鼠模型中的治疗效果。本研究所有统计分析均采用SPSS 17.0和GraphPad软件。 SMSC-Exos 增强骨关节炎软骨细胞的增殖和迁移并抑制其凋亡，但对 ECM 分泌没有影响。 miR-155-5p过表达的外泌体在体外表现出外泌体的共同特征，并通过靶向Runx2进一步促进ECM分泌。因此，SMSC-155-5p-Exos 促进骨关节炎软骨细胞的增殖和迁移，抑制细胞凋亡并增强骨关节炎软骨细胞的 ECM 分泌，并有效预防小鼠模型中的 OA。此外，Runx2 的过度表达部分逆转了 SMSC-155-5p-Exos 对骨关节炎软骨细胞的影响。鉴于 SMSC-Exos 对骨关节炎软骨细胞 ECM 分泌的作用不足，我们修改了 SMSM-Exos 并证明 SMSC-155-5p-Exos 可以预防 OA。源自改良 SMSC 的外泌体可能是预防 OA 的新治疗策略。