The bone marrow is one of the target tissues for titanium dioxide nanoparticles (TiO2NP) following environmental exposure. At present, the consequences of TiO2NP exposure in bone are not well known. The aim of this study was to investigate the effects of TiO2NP on mesenchymal stem cells (MSCs) and potential underlying mechanisms. Mesenchymal bone marrow-derived cells were cultured and treated with various concentrations of TiO2NP. Results showed that TiO2NP incubation produced cytotoxicity as evidenced by reduced cell viability. Using Western blotting TiO2NP was found to increase autophagy as determined by elevation in ratio of LC3-II from LC3-I without evidence of necrotic cell death as estimated by lactic dehydrogenase (LDH) level. TiO2NP produced a rise in intracellular reactive oxygen species (ROS) levels. The observed alterations in autophagy and oxidant stress were associated with upregulation of protein expression of p38, JNK, and ERK. Data indicate that TiO2NP-mediated decrease in MSC survival involves a complex series of events associated stimulation of mitogen-activated protein kinase (MAPK) pathway and consequent autophagy and oxidative damage.

中文翻译：

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二氧化钛纳米颗粒（TiO2NP）诱导间充质干细胞（MSC）自噬的分子机制。

骨髓是环境暴露后二氧化钛纳米粒子（TiO2NP）的目标组织之一。目前，骨骼中TiO2NP暴露的后果尚不清楚。这项研究的目的是研究TiO2NP对间充质干细胞（MSCs）的影响及其潜在的潜在机制。培养骨髓间充质来源的细胞，并用各种浓度的TiO2NP处理。结果表明，TiO2NP孵育可产生细胞毒性，如细胞活力降低所证明。通过蛋白质印迹，发现TiO2NP可以增加自噬，这是通过提高LC3-II与LC3-I的比例来确定的，而没有通过乳酸脱氢酶（LDH）水平估计的坏死细胞死亡的证据。TiO2NP导致细胞内活性氧（ROS）水平升高。观察到的自噬和氧化应激的变化与p38，JNK和ERK蛋白表达的上调有关。数据表明，TiO2NP介导的MSC存活率下降涉及一系列复杂的事件，这些事件与促有丝分裂原激活的蛋白激酶（MAPK）途径的刺激以及随之而来的自噬和氧化损伤有关。