Zhang Gejing, Zhen Chenxiao, Yang Jiancheng, Zhang Zheyuan, Wu Youde, Che Jingmin, Shang Peng
School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, China.
Research & Development Institute of Northwestern Polytechnical University, Shenzhen, 518057, China.
J Orthop Translat. 2022 Nov 3;38:126-140. doi: 10.1016/j.jot.2022.10.007. eCollection 2023 Jan.
OBJECTIVE: With the deepening of magnetic biomedical effects and electromagnetic technology, some medical instruments based on static magnetic field (SMF) have been used in orthopedic-related diseases treatment. Studies have shown SMF could combat osteoporosis by regulating the differentiation of mesenchymal stem cells (MSCs), osteoblast and osteoclast. With the development of nanotechnology, iron oxide nanoparticles (IONPs) have been reported to regulate the process of bone anabolism. As for SMF combined with IONPs, studies indicated osteogenic differentiation of MSCs were promoted by the combination of SMF and IONPs. However, there are few reports on the effects of SMF combined with IONPs on osteoclast. Herein, the purpose of this study was to investigate the effects of high static magnetic field (HiSMF) combined with IONPs on unloading-induced bone loss and osteoclastic formation , and elucidated the potential molecular mechanisms. METHODS: , C57BL/6 J male mice were unloaded via tail suspension or housed normally. The hindlimb of mice were fixed and exposed to 1-2 T SMF for 1 h every day, 10 mg/kg of Ferumoxytol or saline were injected by tail vein once a week, last for 4 weeks. Bone microstructure, mechanical properties, and osteoclastogenesis were examined respectively. , the RAW264.7 cells were used to assess the effects of 1-2 T SMF combined with IONPs in osteoclastogenesis. The iron content was detected by atomic absorption spectrometry and Prussian blue staining. DCFH-DA and MitoSOX™ fluorescence staining were used to assess oxidative stress levels. NF-κB and MAPK signaling pathways were examined by western blot assay. RESULTS: , the results showed 1-2 T SMF and IONPs prevented the damage to bone microstructure and improved the mechanical properties, diminished the number of osteoclasts in unloaded mice, 1-2 T SMF combined with IONPs was found more effective. The iron content in the liver and spleen was reduced by the combination of 1-2 T SMF and IONPs, enhancing iron levels in the femur. osteoclast formation was inhibited by 1-2 T SMF and IONPs treatment, and 1-2 T SMF combined with IONPs had a more pronounced effect. Moreover, iron uptake of IONPs in osteoclast was reduced to 1-2 T SMF exposure. Oxidative stress levels were decreased in osteoclast differentiation under 1-2 T SMF combined with IONPs treatment. Molecularly, the expression of NF-κB and MAPK signaling pathways were inhibited under 1-2 T SMF combined with IONPs in osteoclastogenesis. CONCLUSIONS: Synthetically, our research illustrated 1-2 T SMF combined with IONPs prevented unloading-induced bone loss by regulating iron metabolism in osteoclastogenesis.: As a non-invasive alternative therapy, some medical instruments based on SMF have been used for orthopedic-related diseases treatment for their portability, cheapness and safety. Ferumoxytol (Feraheme™), the first FDA-approved IONP drug for the treatment of iron deficiency anemia, has been also adapted in translational research for osteoporosis. Based on the above-mentioned two points, we found the synergistic effects of SMF and Ferumoxytol for treatment of experimental osteoporosis. These results show translational potentials for clinical application.
目的：随着磁生物医学效应和电磁技术的不断深入，一些基于静磁场（SMF）的医疗器械已被用于骨科相关疾病的治疗。研究表明，SMF可通过调节间充质干细胞（MSCs）、成骨细胞和破骨细胞的分化来对抗骨质疏松症。随着纳米技术的发展，有报道称氧化铁纳米颗粒（IONPs）可调节骨合成代谢过程。至于SMF与IONPs联合应用，研究表明SMF与IONPs联合可促进MSCs的成骨分化。然而，关于SMF与IONPs联合对破骨细胞影响的报道较少。因此，本研究的目的是探讨高静磁场（HiSMF）与IONPs联合对失重诱导的骨质流失和破骨细胞形成的影响，并阐明其潜在的分子机制。 方法：将C57BL/6 J雄性小鼠通过尾部悬吊使其处于失重状态或正常饲养。小鼠后肢固定，每天暴露于1-2 T的SMF中1小时，每周通过尾静脉注射10 mg/kg的菲洛肟铁或生理盐水，持续4周。分别检测骨微结构、力学性能和破骨细胞生成情况。此外，使用RAW264.7细胞评估1-2 T SMF与IONPs联合对破骨细胞生成的影响。通过原子吸收光谱法和普鲁士蓝染色检测铁含量。使用DCFH-DA和MitoSOX™荧光染色评估氧化应激水平。通过蛋白质免疫印迹法检测NF-κB和MAPK信号通路。 结果：结果显示，1-2 T SMF和IONPs可防止骨微结构损伤，改善力学性能，减少失重小鼠破骨细胞数量，发现1-2 T SMF与IONPs联合应用更有效。1-2 T SMF与IONPs联合可降低肝脏和脾脏中的铁含量，提高股骨中的铁水平。1-2 T SMF和IONPs处理可抑制破骨细胞形成，1-2 T SMF与IONPs联合效果更显著。此外，1-2 T SMF暴露可降低破骨细胞对IONPs的铁摄取。1-2 T SMF与IONPs联合处理可降低破骨细胞分化过程中的氧化应激水平。在分子水平上，1-2 T SMF与IONPs联合可抑制破骨细胞生成过程中NF-κB和MAPK信号通路的表达。 结论：综合来看，我们的研究表明1-2 T SMF与IONPs联合通过调节破骨细胞生成中的铁代谢来预防失重诱导的骨质流失。作为一种非侵入性替代疗法，一些基于SMF的医疗器械因其便携性、廉价性和安全性已被用于骨科相关疾病的治疗。菲洛肟铁（Feraheme™）是首个获得美国食品药品监督管理局（FDA）批准用于治疗缺铁性贫血的IONP药物，也已应用于骨质疏松症的转化研究。基于上述两点，我们发现了SMF与菲洛肟铁在治疗实验性骨质疏松症中的协同作用。这些结果显示了其临床应用的转化潜力。
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