Osteoarthritis (OA) is a common degenerative joint disease that affects people worldwide. The interaction between fibroblast-like synoviocytes (FLSs) and chondrocytes may play a vital role in OA disease pathology. However, the underlying mechanisms by which FLSs exert regulatory effects on chondrocytes still need to be elucidated. Exosomes, small membrane vesicles secreted from living cells, are known to play a variety of roles in mediating cell-to-cell communication through the transferring of biological components such as non-coding RNAs and proteins. Here, we investigate the cellular processes of chondrocytes regulated by FLS-derived exosomes and the mechanisms of action underlying the functions of exosomes in OA pathogenesis. We observed that exosome-mediated cartilage repair was characterized by increased cell viability and migration as well as alleviated matrix degradation. Using chondrocyte cultures, the enhanced cellular proliferation and migration during exosome-mediated cartilage repair was linked to the exosomal lncRNA H19-mediated regulation of the miR-106b-5p/TIMP2 axis. Transfection of miR-106-5p mimics in chondrocytes significantly decreased cell proliferation and migration, promoted matrix degradation characterized by elevated MMP13 and ADAMTS5 expression, and reduced the expression of COL2A1 and ACAN in chondrocytes. Furthermore, we found that TIMP2 was directly regulated by miR-106-5p. Co-transfections of miR-106-5p mimics and TIMP2 resulted in higher levels of COL2A1 and ACAN, but lower levels of MMP13 and ADAMTS5. Together, these observations demonstrated that the lncRNA H19 may promote chondrocyte proliferation and migration and inhibit matrix degradation in OA possibly by targeting the miR-106b-5p/TIMP2 axis. In the future, H19 may serve as a potential therapeutic target for the treatment of OA.

骨关节炎 (OA) 是一种常见的退行性关节疾病，影响着全世界的人们。成纤维细胞样滑膜细胞 (FLSs) 和软骨细胞之间的相互作用可能在 OA 疾病病理学中起重要作用。然而，FLSs 对软骨细胞发挥调节作用的潜在机制仍有待阐明。外泌体是活细胞分泌的小膜泡，已知通过转移非编码 RNA 和蛋白质等生物成分在介导细胞间通讯中发挥多种作用。在这里，我们研究了由 FLS 衍生的外泌体调节的软骨细胞的细胞过程以及外泌体在 OA 发病机制中的作用机制。我们观察到外泌体介导的软骨修复以增加细胞活力和迁移以及减轻基质降解为特征。使用软骨细胞培养物，外泌体介导的软骨修复过程中增强的细胞增殖和迁移与外泌体 lncRNA H19 介导的 miR-106b-5p/TIMP2 轴调节有关。在软骨细胞中转染 miR-106-5p 模拟物可显着降低细胞增殖和迁移，促进以 MMP13 和 ADAMTS5 表达升高为特征的基质降解，并降低软骨细胞中 COL2A1 和 ACAN 的表达。此外，我们发现 TIMP2 直接受 miR-106-5p 调节。miR-106-5p 模拟物和 TIMP2 的共转染导致更高水平的 COL2A1 和 ACAN，但更低水平的 MMP13 和 ADAMTS5。一起，这些观察结果表明，lncRNA H19 可能通过靶向 miR-106b-5p/TIMP2 轴促进软骨细胞增殖和迁移并抑制 OA 中的基质降解。未来，H19 可能成为治疗 OA 的潜在治疗靶点。