Wei Fei, Neal Craig J, Sakthivel Tamil Selvan, Kean Thomas, Seal Sudipta, Coathup Melanie J
Biionix Cluster, Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, FL, USA.
Advanced Materials Processing and Analysis Centre, Nanoscience Technology Center (NSTC), Materials Science and Engineering, College of Medicine, University of Central Florida, Orlando, FL, USA.
Mater Sci Eng C Mater Biol Appl. 2021 May;124:112041. doi: 10.1016/j.msec.2021.112041. Epub 2021 Mar 24.
Oxidative stress increases bone loss and limits repair, in part, through immunoregulation and the formation and maintenance of low-grade chronic inflammation. The aim of this study was to investigate the effect of cerium oxide nanoparticles (CeONPs) on (i) macrophage phenotype and cytokine expression under normal and simulated acute and chronic inflammatory conditions and, (ii) human mesenchymal stem cell (hBMSCs) proliferation, osteoinduction and osteogenic differentiation. Spherical particles composed of 60% Ce with a hydrodynamic size of ~35 nm and surface charge of 25.4 mV were internalized within cells. Under both acute and chronic conditions, inducible nitric oxide synthase (iNOS) activity decreased with a significant reduction seen in the 1 and 10 μg/mL groups (p < 0.001). A dose dependent and significant increase in anti-inflammatory cytokine gene expression was observed in all CeONP groups under chronic inflammatory condition. No increase in alkaline phosphatase (ALP) activity or mineral deposits were measured following hBMSCs cultured without osteogenic media in any of the CeONP groups, however, a significant increase in osteogenic-related gene expression, ALP activity and bone mineral deposits was measured when supplemented with both CeONPs and osteogenic media. CeONP activity was multifaceted and exhibited low toxicity. A therapeutic dose of 1 μg/mL delivered a disparate but protective effect when under both acute and chronic inflammatory conditions while at the same dose, potentiated osteogenesis.
氧化应激会增加骨质流失并限制修复，部分原因是通过免疫调节以及低度慢性炎症的形成和维持。本研究的目的是调查氧化铈纳米颗粒（CeONPs）对（i）正常及模拟急性和慢性炎症条件下巨噬细胞表型和细胞因子表达，以及（ii）人间充质干细胞（hBMSCs）增殖、骨诱导和成骨分化的影响。由60%铈组成、流体动力学尺寸约为35 nm且表面电荷为25.4 mV的球形颗粒被细胞内化。在急性和慢性条件下，诱导型一氧化氮合酶（iNOS）活性均降低，在1和10 μg/mL组中显著降低（p < 0.001）。在慢性炎症条件下，所有CeONP组均观察到抗炎细胞因子基因表达呈剂量依赖性显著增加。在任何CeONP组中，未添加成骨培养基培养的hBMSCs后，未检测到碱性磷酸酶（ALP）活性或矿物质沉积增加，然而，当同时添加CeONPs和成骨培养基时，则检测到成骨相关基因表达、ALP活性和骨矿物质沉积显著增加。CeONP活性具有多方面性且毒性较低。在急性和慢性炎症条件下，1 μg/mL的治疗剂量均产生了不同但具有保护作用，并在相同剂量下增强成骨作用。
