Institute of Stomatology, Medical School of Chinese PLA, Beijing, 100853, China.
J Nanosci Nanotechnol. 2020 Mar 1;20(3):1417-1424. doi: 10.1166/jnn.2020.17158.
As a bone implant material, porous tantalum (Ta) has better corrosion resistance and more suitable elastic modulus than titanium. Surface nanomodification can accelerate the integration of Ta implants with bone tissue, which has broad application prospects in the field of dental implantology. Due to mechanical stress and load wear, nanoscale Ta fragments are inevitably exfoliated from the implant surface and brought into direct contact with osteoblasts surrounding the implant. These wear fragments may affect the biological characteristics of osteoblasts and thus the stability of implants. To date, the interaction of nanoscale Ta fragments with osteoblasts has not been clearly investigated. In the current study, we used the mouse osteoblast cell line MC3T3-E1 to explore the effects of Ta nanoparticles (Ta-NPs) on the cytotoxicity, oxidative stress and autophagy of osteoblasts. We found that a low concentration (12.5 g/mL) of Ta-NPs can promote the proliferation of osteoblasts, while the Ta-NPs began to induce a decrease in cell viability at concentrations ≥25 g/mL. Increased cell mortality, reactive oxygen species (ROS) production and decreased mitochondrial membrane potential (MMP) occurred in a dose-dependent manner after Ta-NP treatment. Moreover, with Ta-NP stimulation, the ratio of LC3-II/LC3-I increased, and the level of p62 protein was reduced. However, the degradation of p62 was not continuously increased when the concentration of Ta-NPs was ≥25 g/mL. These results indicate that Ta-NPs induced osteoblast damage via oxidative stress. Autophagy activation may be a key factor in the cellular response to Ta-NP toxicity and could have an important impact on determining the survival or death of osteoblasts.
作为一种骨植入材料，多孔钽（Ta）的耐腐蚀性优于钛，弹性模量也更合适。表面纳米改性可以加速 Ta 植入物与骨组织的整合，在牙科植入物领域具有广阔的应用前景。由于机械应力和负载磨损，纳米级 Ta 碎片不可避免地从植入物表面剥落，并直接与植入物周围的成骨细胞接触。这些磨损碎片可能会影响成骨细胞的生物学特性，从而影响植入物的稳定性。迄今为止，纳米级 Ta 碎片与成骨细胞的相互作用尚未得到明确研究。在本研究中，我们使用小鼠成骨细胞系 MC3T3-E1 来研究 Ta 纳米颗粒（Ta-NPs）对成骨细胞的细胞毒性、氧化应激和自噬的影响。我们发现，低浓度（12.5μg/ml）的 Ta-NPs 可促进成骨细胞的增殖，而 Ta-NPs 在浓度≥25μg/ml 时开始诱导细胞活力下降。Ta-NP 处理后，细胞死亡率增加、活性氧（ROS）生成增加和线粒体膜电位（MMP）降低呈剂量依赖性。此外，在 Ta-NP 刺激下，LC3-II/LC3-I 的比值增加，p62 蛋白水平降低。然而，当 Ta-NPs 的浓度≥25μg/ml 时，p62 的降解并没有持续增加。这些结果表明 Ta-NPs 通过氧化应激诱导成骨细胞损伤。自噬激活可能是细胞对 Ta-NP 毒性反应的关键因素，并可能对决定成骨细胞的存活或死亡具有重要影响。
