Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia.
Chair of Medical and Molecular Genetics Research, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia.
Int J Nanomedicine. 2021 Jan 13;16:331-343. doi: 10.2147/IJN.S285233. eCollection 2021.
Redox homeostasis plays an important role in the osteogenic differentiation of human mesenchymal stem cells (hMSCs) for bone engineering. Oxidative stress (OS) is believed to induce osteoporosis by changing bone homeostasis. Selenium nanoparticles (SeNPs), an antioxidant with pleiotropic pharmacological activity, prevent bone loss. However, the molecular mechanism underlying the osteogenic activity during hMSC-SeNP interaction is unclear.
This study assessed the effects of different concentrations (25, 50, 100, and 300 ng/mL) of SeNPs on the cell viability and differentiation ability of human embryonic stem cell-derived hMSCs. In addition, we analyzed OS markers and their effect on mitogen-activated protein kinase (MAPK) and Forkhead box O3 (FOXO3) during osteogenesis.
SeNPs increased the cell viability of hMSCs and induced their differentiation toward an osteogenic over an adipogenic lineage by enhancing osteogenic transcription and mineralization, while inhibiting Nile red staining and adipogenic gene expression. By preventing excessive reactive oxygen species accumulation, SeNPs increased antioxidant levels in hMSCs undergoing osteogenesis compared to untreated cells. In addition, SeNPs significantly upregulated the gene and protein expression of phosphorylated c-Jun N-terminal kinase (JNK) and FOXO3a, with no significant change in the expression levels of extracellular signal-related kinase (ERK) and p38 MAPK.
The results approved that low concentrations of SeNPs might enhance the cell viability and osteogenic potential of hMSCs by moderating OS. Increased JNK and FOXO3a expression shows that SeNPs might enhance osteogenesis via activation of the JNK/FOXO3 pathway. In addition, SeNP co-supplementation might prevent bone loss by enhancing osteogenesis and, thus, can be an effective candidate for treating osteoporosis through cell-based therapy.
氧化还原平衡在人骨髓间充质干细胞（hMSCs）的成骨分化中起着重要作用，对于骨工程学而言更是如此。氧化应激（OS）被认为通过改变骨稳态来诱导骨质疏松症。硒纳米粒子（SeNPs）作为一种具有多种药理学活性的抗氧化剂，可以防止骨质流失。然而，hMSC-SeNP 相互作用过程中成骨活性的分子机制尚不清楚。
本研究评估了不同浓度（25、50、100 和 300ng/ml）的 SeNPs 对人胚胎干细胞衍生的 hMSCs 细胞活力和分化能力的影响。此外，我们分析了 OS 标志物及其在成骨过程中对丝裂原活化蛋白激酶（MAPK）和叉头框蛋白 O3（FOXO3）的影响。
SeNPs 增加了 hMSCs 的细胞活力，并通过增强成骨转录和矿化，使 hMSCs 向成骨分化而不是向脂肪生成谱系分化，同时抑制尼罗红染色和脂肪生成基因表达。与未处理的细胞相比，SeNPs 通过防止活性氧（ROS）过度积累，增加了成骨 hMSCs 中的抗氧化水平。此外，SeNPs 显著上调了磷酸化 c-Jun N-末端激酶（JNK）和 FOXO3a 的基因和蛋白表达，而细胞外信号调节激酶（ERK）和 p38 MAPK 的表达水平没有显著变化。
结果表明，低浓度的 SeNPs 可能通过调节 OS 来增强 hMSCs 的细胞活力和成骨潜能。JNK 和 FOXO3a 表达的增加表明，SeNPs 可能通过激活 JNK/FOXO3 通路增强成骨作用。此外，SeNP 联合补充可能通过增强成骨作用来预防骨质流失，因此可以作为通过细胞治疗治疗骨质疏松症的有效候选药物。
