Constitutive photomorphogenic 1 (COP1), is an E3 ubiquitin ligase that plays a role in the regulation of various cellular processes including cell growth, differentiation, and survival in mammals. In certain conditions such as overexpression or loss of function, COP1 acts either as an oncogenic protein or as a tumor suppressor by targeting specific proteins for ubiquitination-mediated degradation. However, the precise role of COP1 has not been well studied in primary articular chondrocytes. In this study, we investigated the role of COP1 in chondrocyte differentiation. Western blotting and reverse transcription-polymerase chain reaction analysis demonstrated that COP1 overexpression reduced type II collagen expression, promoted cyclooxygenase 2 (COX-2) expression, and reduced sulfated proteoglycan synthesis, as detected by Alcian blue staining. Upon siRNA treatment, revived type II collagen, sulfated proteoglycan production, and decreased COX-2 expression. Phosphorylation of p38 kinase and ERK-1/-2 signaling pathways was regulated by COP1 upon cDNA and siRNA transfection in chondrocytes. The inhibition of the p38 kinase and ERK-1/-2 signaling pathways with SB203580 and PD98059 ameliorated the expression of type II collagen and COX-2 in transfected chondrocytes, thus suggesting that COP1 regulates differentiation and inflammation in rabbit articular chondrocytes via the p38 kinase and ERK-1/-2 signaling pathway.

中文翻译：

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E3 泛素连接酶组成型光形态发生 1 通过 MAPK 信号通路调节兔关节软骨细胞的分化和炎症。

本构光形态发生 1 (COP1) 是一种 E3 泛素连接酶，在哺乳动物的各种细胞过程（包括细胞生长、分化和存活）的调节中发挥作用。在某些情况下，例如过度表达或功能丧失，COP1 通过靶向特定蛋白质进行泛素化介导的降解，充当致癌蛋白或肿瘤抑制因子。然而，COP1 在原代关节软骨细胞中的确切作用尚未得到很好的研究。在这项研究中，我们研究了 COP1 在软骨细胞分化中的作用。蛋白质印迹和逆转录聚合酶链反应分析表明，COP1 过表达减少了 II 型胶原蛋白的表达，促进了环氧合酶 2 (COX-2) 的表达，并减少了硫酸化蛋白多糖的合成，如阿尔新蓝染色所检测的那样。在 siRNA 处理后，恢复了 II 型胶原蛋白、硫酸化蛋白多糖的产生，并降低了 COX-2 的表达。在软骨细胞中转染 cDNA 和 siRNA 后，p38 激酶和 ERK-1/-2 信号通路的磷酸化受 COP1 调节。SB203580 和 PD98059 对 p38 激酶和 ERK-1/-2 信号通路的抑制改善了转染软骨细胞中 II 型胶原蛋白和 COX-2 的表达，因此表明 COP1 通过 p38 激酶调节兔关节软骨细胞的分化和炎症和 ERK-1/-2 信号通路。