Proliferation of rabbit chondrocyte and inhibition of IL-1beta-induced apoptosis through MEK/ERK signaling by statins.
Proliferation of rabbit chondrocyte and inhibition of IL-1beta-induced apoptosis through MEK/ERK signaling by statins.
复制标题
他汀类药物通过 MEK/ERK 信号传导促进兔软骨细胞增殖并抑制 IL-1β 诱导的细胞凋亡。
DOI：
10.1007/s11626-016-0086-1
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Zhang Xiaolei
中科院分区：
文献类型：
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作者：
Zhou Bin;Chen Deheng;Xu Huazi;Zhang Xiaolei
软骨细胞通过维持软骨基质在软骨内骨化和软骨修复中起着关键作用。他汀类药物已被广泛用于降低心血管疾病患者的胆固醇水平。以前的研究已经证明了他汀类药物在软骨细胞增殖中的潜在作用。本研究旨在探讨洛伐他汀对兔软骨细胞增殖的调控作用及其信号转导机制，从而探索其在软骨细胞相关疾病如软骨损伤和骨关节炎中的应用前景。用不同浓度的洛伐他汀处理兔软骨细胞，CCK-8法检测细胞增殖率。结果显示，在洛伐他汀处理下，软骨细胞增殖显著增加。实时荧光定量PCR检测发现，洛伐他汀处理后，COL 2A 1、SOX-9、Caspase-3和MMP-3基因的表达水平发生了显著变化。Western blotting分析显示，洛伐他汀处理对COL 2A 1、SOX-9、MEK 1/2、p-MEK 1/2、ERK 1/2、p-ERK 1/2、Caspase-3和MMP-3蛋白的丰度也有显著影响。白细胞介素-1 β（IL-1β）通过诱导关节软骨和软骨细胞老化和衰老参与骨关节炎（OA）的进展。在本研究中，我们观察到洛伐他汀处理抑制IL-1β诱导的软骨细胞凋亡，而洛伐他汀和U 0126联合处理明显抵消了洛伐他汀对软骨细胞增殖的凋亡抑制作用。COL 2A 1、SOX-9、MEK 1/2、p-MEK 1/2、ERK 1/2、p-ERK 1/2、caspase-3和MMP-3基因的表达水平和蛋白丰度在联合处理下均发生显著变化。以上结果提示，洛伐他汀可显著促进软骨细胞增殖，抑制IL-1β诱导的软骨细胞凋亡，这一作用是通过MEK/ERK信号通路介导的。
Chondrocyte plays a critical role in endochondral ossification and cartilage repair by maintaining the cartilaginous matrix. Statins have been widely used to lower the cholesterol level in patients with cardiovascular disorders. Previous research has demonstrated potential role of statins in chondrocyte proliferation. This study addresses the proliferation-regulatory effect of lovastatin in rabbit chondrocytes as well as the underlying signaling mechanisms, thereby exploring its potential application in chondrocyte-related disorders, such as cartilage damage and osteoarthritis. Rabbit chondrocytes were treated with lovastatin at multiple concentrations, and the proliferation rate was measured by CCK-8 test. The results showed significant increase in chondrocyte proliferation under lovastatin treatment. Using real-time quantitative PCR, it was observed that the expression levels of COL2A1, SOX-9, Caspase-3, and MMP-3 genes were significantly changed by lovastatin treatment. Western blotting analysis showed that the abundance of COL2A1, SOX-9, MEK1/2, p-MEK1/2, ERK1/2, p-ERK1/2, Caspase-3, and MMP-3 proteins was also significantly influenced by lovastatin treatment. Interleukine-1 beta (IL-1β) is involved in the progression of osteoarthritis (OA) by inducing articular cartilage and chondrocyte aging and senescence. In this study, we observed that lovastatin treatment inhibited IL-1β-induced chondrocyte apoptosis, while the combined treatment of lovastatin and U0126 evidently offset the apoptosis-inhibiting effect of lovastatin in chondrocyte proliferation. The expressional level and protein abundance of COL2A1, SOX-9, MEK1/2, p-MEK1/2, ERK1/2, p-ERK1/2, caspase-3, and MMP-3 genes showed significant alterations under the combined treatment. Together, our results suggested that lovastatin significantly promoted proliferation and inhibited the IL-1β-induced apoptosis in rabbit chondrocytes, which was mediated by the MEK/ERK signaling.