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With the development of biotechnology, biomaterials have been rapidly developed and shown great potential in bone regeneration therapy and bone tissue engineering. Nanoparticles have attracted the attention of researches and have applied in various fields especially in the biomedical field as the special physicochemical properties. Nanoparticles were found to regulate bone remodeling depending on their size, shape, composition, and charge. Therefore, in-depth research was necessary to provide the basic support to select the most suitable nanoparticles for bone relate diseases treatment. This article reviews the current development of nanoparticles in bone tissue engineering, focusing on drug delivery, gene delivery, and cell labeling. In addition, the research progress on the interaction of nanoparticles with bone cells, focusing on osteoblasts, osteoclasts, and bone marrow mesenchymal stem cells, and the underlying mechanism were also reviewed. Finally, the current challenges and future research directions are discussed. Thus, detailed study of nanoparticles may reveal new therapeutic strategies to improve the effectiveness of bone regeneration therapy or other bone diseases., Competing Interests: The authors declare no conflicts of interest for this work., (This journal is © The Royal Society of Chemistry.)

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 in vivo and osteoclastic formation in vitro , and elucidated the potential molecular mechanisms., Methods: In vivo , 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. In vitro , 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: In vivo , 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. In vitro, 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. Translational potential of this article : 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., Competing Interests: No potential conflict of interest was reported by the authors., (© 2022 The Authors.)