Selenium protects against LPS-induced MC3T3-E1 cells apoptosis through modulation of microRNA-155 and PI3K/Akt signaling pathways

Abstract Bone infection or osteomyelitis is usually a complication of inflammation-related traumatic bone injury. Selenium has been shown to have potential cytoprotective effects and the ability to reduce oxidative stress and apoptotic events in osteomyelitis, but the exact mechanism remains unclear. Here, we used LPS-induced apoptotic MC3T3-E1 cells and aimed to confirm selenium's protective effect on cell apoptosis as well as to investigate the underlying mechanisms of this role. Our investigation confirmed selenium-mediated inhibition of LPS-induced cell apoptosis and ROS accumulation in MC3T3-E1 cells. Upon selenium treatment, the bcl-2 levels were upregulated, while the levels of Bax and cyto-C were down-regulated. Furthermore, these effects were accompanied by the suppression of miR-155 and the phosphorylation of protein kinase B (Akt). A more in-depth study demonstrated that LY294002 (a specific inhibitor of PI3K), abolished the selenium-mediated cytoprotective effect of MC3T3-E1 cells against LPS-induced injury and down-regulation of miR-155. In general, these results demonstrated that selenium exerts a cytoprotective effect by attenuating cell apoptosis and oxidative damage via a PI3K/Akt/miR-155-dependent mechanism.

摘要 骨感染或骨髓炎（osteomyelitis）通常是炎症相关创伤性骨损伤的并发症。已有研究表明，硒具有潜在的细胞保护作用，能够减轻骨髓炎中的氧化应激与细胞凋亡事件，但其确切的作用机制仍未阐明。本研究使用脂多糖（LPS）诱导的MC3T3-E1细胞，旨在验证硒对细胞凋亡的保护作用，并探究该作用的潜在分子机制。本研究证实，硒可抑制LPS诱导的MC3T3-E1细胞凋亡与活性氧（ROS）积累。经硒处理后，B细胞淋巴瘤-2（Bcl-2）的表达水平上调，而Bcl-2相关X蛋白（Bax）与细胞色素C（cyto-C）的表达水平下调。此外，这些效应伴随微小RNA-155（miR-155）的表达抑制以及蛋白激酶B（Akt）的磷酸化。进一步的深入研究表明，LY294002（一种磷脂酰肌醇3-激酶（PI3K）的特异性抑制剂）可抵消硒介导的MC3T3-E1细胞抗LPS损伤的细胞保护作用，同时阻断硒诱导的miR-155下调。综上，本研究结果表明，硒通过依赖于PI3K/Akt/miR-155的信号通路，减轻细胞凋亡与氧化损伤，从而发挥细胞保护作用。