Background: Release of metallic wear particles from hip replacement implants is closely associated with aseptic loosening that affects the functionality and survivorship of the prostheses. Chromium oxide nanoparticles (CrNPs) are the dominant form of the wear particles found in the periprosthetic tissues. Whether CrNPs play a role in the clinically observed particle-induced osteolysis, tissue inflammatory reactions and functional activities of human mesenchymal stem cells (MSCs) remain unknown.
Methods: A tibia-defect rat model, cytotoxicity assays and flow cytometry were applied to study the effect of CrNPs on MSCs survival and macrophage inflammatory response. Also, oscillatory fluid flow stimulation was used to analyse the osteogenic differentiation of MSCs while treated by CrNPs. In addition, the influence of CrNPs on MSC biomechanical properties was determined via atomic force microscope (AFM) and fluorescence microscopy.
Results: It was found that implantation of CrNPs significantly decreased bone formation in vivo. CrNPs had no obvious effects on inflammatory cytokines release of U937 macrophages. Additionally, CrNPs did not interfere with MSCs osteogenic differentiation under static culture. However, the upregulated osteogenic differentiation of MSCs due to fluid flow stimulation was reduced by CrNPs in a dose-dependent manner. Moreover, osteogenic gene expression of OPN, Cox2 and Rnux2 after mechanical stimulation was also decreased by CrNPs treatments. Furthermore, cell elasticity and adhesion force of MSCs were affected by CrNPs over 3 days of exposure. We further verified that these effects of CrNPs could be associated with its interruption on cell mechanical properties.
Conclusion: The results demonstrated that CrNPs impaired cellular response to mechanical stimulus and osteogenesis without noticeable effects on the survival of the human MSCs.



中文翻译：

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氧化铬纳米颗粒损害成骨和细胞对机械刺激的反应

背景：髋关节置换植入物中金属磨损颗粒的释放与影响假体功能和存活率的无菌性松动密切相关。氧化铬纳米颗粒 (CrNPs) 是在假体周围组织中发现的主要磨损颗粒形式。CrNPs是否在临床观察到的颗粒诱导的骨溶解、组织炎症反应和人间充质干细胞（MSCs）的功能活动中发挥作用仍然未知。
方法：应用胫骨缺损大鼠模型、细胞毒性测定和流式细胞术研究 CrNPs 对 MSCs 存活和巨噬细胞炎症反应的影响。此外，振荡流体流动刺激用于分析 MSCs 在 CrNPs 治疗时的成骨分化。此外，通过原子力显微镜 (AFM) 和荧光显微镜确定 CrNPs 对 MSC 生物力学性能的影响。
结果：发现CrNPs的植入显着降低了体内骨形成。CrNPs对U937巨噬细胞炎性细胞因子的释放无明显影响。此外，在静态培养下，CrNPs 不会干扰 MSCs 的成骨分化。然而，由于流体流动刺激而上调的 MSCs 成骨分化被 CrNPs 以剂量依赖性方式降低。此外，CrNPs 处理也降低了机械刺激后 OPN、Cox2 和 Rnux2 的成骨基因表达。此外，MSCs 的细胞弹性和粘附力在 3 天的暴露后受到 CrNPs 的影响。我们进一步证实，CrNPs 的这些影响可能与其对细胞机械性能的中断有关。
结论：结果表明，CrNPs 损害了细胞对机械刺激和成骨的反应，而对人类 MSCs 的存活没有明显影响。