Chondrocyte production of catabolic and inflammatory mediators participating in extracellular matrix degradation has been regarded as a central event in osteoarthritis (OA) development. During OA pathogenesis, interleukin-1β (IL-1β) decreases the mRNA expression and protein levels of transforming growth factor-β receptor type-2 (TGFBR2), thus disrupting transforming growth factor-β signaling and promoting OA development. In the present study, we attempted to identify the differentially expressed genes in OA chondrocytes upon IL-1β treatment, investigate their specific roles in OA development, and reveal the underlying mechanism. As shown by online data analysis and experimental results, TGFBR2 expression was significantly downregulated in IL-1β-treated human primary OA chondrocytes. IL-1β treatment induced degenerative changes in OA chondrocytes, as manifested by increased matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs 5 proteins, decreased Aggrecan and Collagen II proteins, and suppressed OA chondrocyte proliferation. These degenerative changes were significantly reversed by TGFBR2 overexpression. miR-302c expression was markedly induced by IL-1β treatment in OA chondrocytes. miR-302c suppressed the expression of TGFBR2 via direct binding to its 3′- untranslated region. Similar to TGFBR2 overexpression, miR-302c inhibition significantly improved IL-1β-induced degenerative changes in OA chondrocytes. Conversely, TGFBR2 silencing enhanced IL-1β-induced degenerative changes and significantly reversed the effects of miR-302c inhibition in response to IL-1β treatment. In conclusion, the miR-302c/TGFBR2 axis could modulate IL-1β-induced degenerative changes in OA chondrocytes and might become a novel target for OA treatment.

参与细胞外基质降解的分解代谢和炎症介质的软骨细胞产生被认为是骨关节炎 (OA) 发展的中心事件。在 OA 发病过程中，白细胞介素-1β (IL-1β) 降低了 2 型转化生长因子-β 受体 (TGFBR2) 的 mRNA 表达和蛋白水平，从而破坏了转化生长因子-β 信号传导并促进了 OA 的发展。在本研究中，我们试图鉴定 IL-1β 处理后 OA 软骨细胞中的差异表达基因，研究它们在 OA 发展中的具体作用，并揭示其潜在机制。如在线数据分析和实验结果所示，在IL-1β处理的人原代OA软骨细胞中TGFBR2表达显着下调。IL-1β 治疗诱导 OA 软骨细胞的退行性变化，如增加的基质金属蛋白酶 13 和具有血小板反应素基序 5 蛋白的去整合素和金属蛋白酶，减少聚集蛋白聚糖和胶原蛋白 II 蛋白，并抑制 OA 软骨细胞增殖。TGFBR2过表达显着逆转了这些退行性变化。IL-1β 处理在 OA 软骨细胞中显着诱导 miR-302c 表达。miR-302c 通过直接结合其 3'-非翻译区来抑制 TGFBR2 的表达。与 TGFBR2 过表达类似，抑制 miR-302c 显着改善 IL-1β 诱导的 OA 软骨细胞退行性变化。相反，TGFBR2 沉默增强了 IL-1β 诱导的退行性变化，并显着逆转了 miR-302c 抑制对 IL-1β 治疗的影响。综上所述，