Dataset Information

A Static Magnetic Field Improves Iron Metabolism and Prevents High-Fat-Diet/Streptozocin-Induced Diabetes.

ABSTRACT: Type 2 diabetes (T2D) is a metabolic disorder with high prevalence and severe complications that has recently been indicated to be treatable by a combined static magnetic field (SMF) and electric field. We systematically compared four types of SMFs and found that a downward SMF of ∼100 mT could effectively reduce the development of hyperglycemia, fatty liver, weight gain, and tissue injury in high-fat-diet (HFD)/streptozocin-induced T2D mice, but not the upward SMF. The downward SMF markedly restored the Bacteroidetes population and reversed the iron complex outer membrane receptor gene reduction in the mice gut microbiota, and reduced iron deposition in the pancreas. SMF also reduced the labile iron and reactive oxygen species level in pancreatic Min6 cells in vitro and prevented palmitate-induced Min6 cell number reduction. Therefore, this simple SMF setting could partially prevent HFD-induced T2D development and ameliorate related symptoms, which could provide a low-cost and non-invasive physical method to prevent and/or treat T2D in the future.

SUBMITTER: Yu B

PROVIDER: S-EPMC8454665 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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A Static Magnetic Field Improves Iron Metabolism and Prevents High-Fat-Diet/Streptozocin-Induced Diabetes.

Yu Biao B Liu Juanjuan J Cheng Jing J Zhang Lei L Song Chao C Tian Xiaofei X Fan Yixiang Y Lv Yue Y Zhang Xin X

Innovation (Cambridge (Mass.)) 20210107 1

Type 2 diabetes (T2D) is a metabolic disorder with high prevalence and severe complications that has recently been indicated to be treatable by a combined static magnetic field (SMF) and electric field. We systematically compared four types of SMFs and found that a downward SMF of ∼100 mT could effectively reduce the development of hyperglycemia, fatty liver, weight gain, and tissue injury in high-fat-diet (HFD)/streptozocin-induced T2D mice, but not the upward SMF. The downward SMF markedly res ...[more]

PMID: 34557734

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Project description:ObjectiveWith 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.MethodsIn 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.ResultsIn 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.ConclusionsSynthetically, 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.

Project description:Many studies have indicated that static magnetic fields (SMFs) have positive effects on bone tissue, including bone formation and bone healing process. Evaluating the effects of SMFs on bone cell (especially osteoblast) function and exploring the mechanism, which is critical for understanding the possible risks or benefits from SMFs to the balance of bone remodeling. Iron and magnetic fields have the natural relationship, and iron is an essential element for normal bone metabolism. Iron overload or deficiency can cause severe bone disorders including osteoporosis. However, there are few reports regarding the role of iron in the regulation of bone formation under SMFs. In this study, hypomagnetic field (HyMF) of 500 nT, moderate SMF (MMF) of 0.2 T, and high SMF (HiMF) of 16 T were used to investigate how osteoblast (MC3T3-E1) responses to SMFs and iron metabolism of osteoblast under SMFs. The results showed that SMFs did not pose severe toxic effects on osteoblast growth. During cell proliferation, iron content of osteoblast MC3T3-E1 cells was decreased in HyMF, but was increased in MMF and HiMF after exposure for 48 h. Compared to untreated control (i.e., geomagnetic field, GMF), HyMF and MMF exerted deleterious effects on osteoblast differentiation by simultaneously retarding alkaline phosphatase (ALP) activity, mineralization and calcium deposition. However, when exposed to HiMF of 16 T, the differentiation potential showed the opposite tendency with enhanced mineralization. Iron level was increased in HyMF, constant in MMF and decreased in HiMF during cell differentiation. In addition, the mRNA expression of transferrin receptor 1 (TFR1) was promoted by HyMF but was inhibited by HiMF. At the same time, HiMF of 16 T and MMF of 0.2 T increased the expression of ferroportin 1 (FPN1). In conclusion, these results indicated that osteoblast differentiation can be regulated by altering the strength of the SMF, and iron is possibly involved in this process.

Project description:BackgroundThe therapeutic potential of exosomes derived from stem cells has attracted increasing interest recently, because they can exert similar paracrine functions of stem cells and overcome the limitations of stem cells transplantation. Exosomes derived from bone mesenchymal stem cells (BMSC-Exos) have been confirmed to promote osteogenesis and angiogenesis. The magnetic nanoparticles (eg. Fe3O4, γ-Fe2O3) combined with a static magnetic field (SMF) has been commonly used to increase wound healing and bone regeneration. Hence, this study aims to evaluate whether exosomes derived from BMSCs preconditioned with a low dose of Fe3O4 nanoparticles with or without the SMF, exert superior pro-osteogenic and pro-angiogenic activities in bone regeneration and the underlying mechanisms involved.MethodsTwo novel types of exosomes derived from preconditioned BMSCs that fabricated by regulating the contents with the stimulation of magnetic nanoparticles and/or a SMF. Then, the new exosomes were isolated by ultracentrifugation and characterized. Afterwards, we conducted in vitro experiments in which we measured osteogenic differentiation, cell proliferation, cell migration, and tube formation, then established an in vivo critical-sized calvarial defect rat model. The miRNA expression profiles were compared among the exosomes to detect the potential mechanism of improving osteogenesis and angiogenesis. At last, the function of exosomal miRNA during bone regeneration was confirmed by utilizing a series of gain- and loss-of-function experiments in vitro.Results50 µg/mL Fe3O4 nanoparticles and a 100 mT SMF were chosen as the optimum magnetic conditions to fabricate two new exosomes, named BMSC-Fe3O4-Exos and BMSC-Fe3O4-SMF-Exos. They were both confirmed to enhance osteogenesis and angiogenesis in vitro and in vivo compared with BMSC-Exos, and BMSC-Fe3O4-SMF-Exos had the most marked effect. The promotion effect was found to be related to the highly riched miR-1260a in BMSC-Fe3O4-SMF-Exos. Furthermore, miR-1260a was verified to enhance osteogenesis and angiogenesis through inhibition of HDAC7 and COL4A2, respectively.ConclusionThese results suggest that low doses of Fe3O4 nanoparticles combined with a SMF trigger exosomes to exert enhanced osteogenesis and angiogenesis and that targeting of HDAC7 and COL4A2 by exosomal miR-1260a plays a crucial role in this process. This work could provide a new protocol to promote bone regeneration for tissue engineering in the future.

Dataset Information

A Static Magnetic Field Improves Iron Metabolism and Prevents High-Fat-Diet/Streptozocin-Induced Diabetes.

Publications

A Static Magnetic Field Improves Iron Metabolism and Prevents High-Fat-Diet/Streptozocin-Induced Diabetes.

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