Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongju, Republic of Korea.
Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongju, Republic of Korea.
Eur J Pharmacol. 2018 Sep 5;834:197-205. doi: 10.1016/j.ejphar.2018.07.016. Epub 2018 Jul 26.
Alterations in cell morphology involve changes in the actin cytoskeleton and play crucial roles in determining chondrocyte phenotypes. Although the effects of simvastatin (SV) have been demonstrated in various cell types, the mechanisms and effects of SV on chondrocyte differentiation and actin cytoskeletal rearrangement are still unclear. Here, we investigated the roles of actin filament rearrangement on SV-induced differentiation of rabbit articular chondrocytes. Treatment with SV caused actin remodeling in comparison with that in untreated chondrocytes, as determined by immunofluorescence staining. Moreover, treatment with cytochalasin D (CD) and jasplakinolide (JAS), which modulate actin filament formation, resulted in reorganization of the actin cytoskeleton compared with that induced by SV in chondrocytes. In addition, CD synergistically enhanced the SV-induced increase in type II collagen expression, whereas JAS dramatically inhibited SV-induced differentiation. We also found that differentiation via SV-dependent actin cytoskeleton changes was regulated by the extracellular signal-regulated kinase (ERK)-1/2 and p38 kinase pathways. These results demonstrated that actin cytoskeletal rearrangement by SV regulated type II collagen expression and suggested that ERK-1/2 and p38 kinase pathways may play important roles in SV-induced type II collagen expression by altering actin cytoskeletal reorganization in rabbit articular chondrocytes.
细胞形态的改变涉及到肌动蛋白细胞骨架的变化，在决定软骨细胞表型方面发挥着关键作用。虽然辛伐他汀（SV）在各种细胞类型中的作用已经得到了证实，但 SV 对软骨细胞分化和肌动蛋白细胞骨架重排的机制和影响仍不清楚。在这里，我们研究了肌动蛋白丝重排在 SV 诱导兔关节软骨细胞分化中的作用。与未处理的软骨细胞相比，用 SV 处理会导致肌动蛋白重塑，这可以通过免疫荧光染色来确定。此外，用细胞松弛素 D（CD）和 Jasplakinolide（JAS）处理，这两种药物可以调节肌动蛋白丝的形成，与 SV 诱导软骨细胞中的肌动蛋白细胞骨架重排相比，会导致肌动蛋白细胞骨架的重新排列。此外，CD 协同增强了 SV 诱导的 II 型胶原表达的增加，而 JAS 则显著抑制了 SV 诱导的分化。我们还发现，通过 SV 依赖的肌动蛋白细胞骨架变化进行的分化受细胞外信号调节激酶（ERK）-1/2 和 p38 激酶途径的调节。这些结果表明，SV 引起的肌动蛋白细胞骨架重排调节 II 型胶原的表达，并表明 ERK-1/2 和 p38 激酶途径可能通过改变兔关节软骨细胞中肌动蛋白细胞骨架的重排，在 SV 诱导的 II 型胶原表达中发挥重要作用。
