Moderate static magnetic field promotes fracture healing and regulates iron metabolism in mice.

BACKGROUND: Fractures are the most common orthopedic diseases. It is known that static magnetic fields (SMFs) can contribute to the maintenance of bone health. However, the effect and mechanism of SMFs on fracture is still unclear. This study is aim to investigate the effect of moderate static magnetic fields (MMFs) on bone structure and metabolism during fracture healing. METHODS: Eight-week-old male C57BL/6J mice were subjected to a unilateral open transverse tibial fracture, and following treatment under geomagnetic field (GMF) or MMF. The micro-computed tomography (Micro-CT) and three-point bending were employed to evaluate the microarchitecture and mechanical properties. Endochondral ossification and bone remodeling were evaluated by bone histomorphometric and serum biochemical assay. In addition, the atomic absorption spectroscopy and ELISA were utilized to examine the influence of MMF exposure on iron metabolism in mice. RESULTS: MMF exposure increased bone mineral density (BMD), bone volume per tissue volume (BV/TV), mechanical properties, and proportion of mineralized bone matrix of the callus during fracture healing. MMF exposure reduced the proportion of cartilage in the callus area during fracture healing. Meanwhile, MMF exposure increased the number of osteoblasts in callus on the 14th day, and reduced the number of osteoclasts on the 28th day of fracture healing. Furthermore, MMF exposure increased PINP and OCN levels, and reduced the TRAP-5b and ß-CTX levels in serum. It was also observed that MMF exposure reduced the iron content in the liver and callus, as well as serum ferritin levels while elevating the serum hepcidin concentration. CONCLUSIONS: MMF exposure could accelerate fracture healing via promote the endochondral ossification and bone formation while regulating systemic iron metabolism during fracture healing. This study suggests that MMF may have the potential to become a form of physical therapy for fractures.

Magneto-mechanical stimulation modulates osteocyte fate via the ECM-integrin-CSK axis and wnt pathway.

Osteocytes are the mechano-sensors of bones. Large gradient high-static magnetic fields (LG-HMFs) produce stable, high-precision, and non-attenuation mechanical forces. We discovered that magnetic forces opposite to gravity inhibited MLO-Y4 osteocyte proliferation and viability by inducing structural damage and apoptosis. In contrast, magnetic force loading in the same direction as that of gravity promoted the proliferation and inhibited apoptosis of MLO-Y4 osteocytes. Differentially expressed gene (DEG) analysis after magnetic force stimulation indicated that the ECM-integrin-CSK axis responded most significantly to mechanical signals. Wisp2 was the most significant DEG between the 12 T upward and downward groups, showing the highest correlation with the Wnt pathway according to the STRING protein interaction database. Explaining the cellular and molecular mechanisms by which mechanical stimuli influence bone remodeling is currently the focus of osteocyte-related research. Our findings provide insights into the effects of LG-HMFs on bone cells, which have further implications in clinical practice.

Exposure to a static magnetic field attenuates hepatic damage and function abnormality in obese and diabetic mice.

Static magnetic fields (SMFs) exhibit significant effect on health care. However, the effect of SMF on hepatic metabolism and function in obesity and diabetes are still unknown. Liver is not only the main site for glucolipid metabolism but also the core part for iron metabolism regulation. Dysregulations of iron metabolism and redox status are risk factors for the development of hepatic injury and affect glucolipid metabolism in obesity and diabetes. Mice of HFD-induced obesity and HFD/streptozocin-induced diabetes were exposed to a moderate-intensity SMF (0.4-0.7 T, direction: upward, 4 h/day, 8 weeks). Results showed that SMF attenuated hepatic damage by decreasing inflammation and fibrosis in obese and diabetic mice. SMF had no effects on improving glucose/insulin tolerance but regulated proteins (GLUT1 and GLUT4) and genes (G6pc, Pdk4, Gys2 and Pkl) participating in glucose metabolism with phosphorylation of Akt/AMPK/GSK3ß. SMF also reduced lipid droplets accumulation through decreasing Plin2 and Plin5 and regulated lipid metabolism with elevated hepatic expressions of PPARγ and C/EBPα in obese mice. In addition, SMF decreased hepatic iron deposition with lower FTH1 expression and modulated systematic iron homeostasis via BMP6-mediated regulation of hepcidin. Moreover, SMF balanced hepatic redox status with regulation on mitochondrial function and MAPKs/Nrf2/HO-1 pathway. Finally, we found that SMF activated hepatic autophagy and enhanced lipophagy by upregulating PNPLA2 expression in obese and diabetic mice. Our results demonstrated that SMF significantly ameliorated the development of hepatic injury in obese and diabetic mice by inhibiting inflammatory level, improving glycolipid metabolism, regulating iron metabolism, balancing redox level and activating autophagy.

12 T high static magnetic field suppresses osteosarcoma cells proliferation by regulating intracellular ROS and iron status.

Many studies indicated that static magnetic fields (SMFs) have anti-cancer effects. However, effect of SMFs on cancer cells with strength exceeding 12 T are rarely reported. The intracellular iron could participate in the reactive oxygen species (ROS) production and affect cell proliferation. This study aimed to investigate the effect of 12 T high static magnetic field (HiSMF) on osteosarcoma cells and the relationship with intracellular iron. The 12 T HiSMF was generated by a superconducting magnet. The proliferation was evaluated by CCK-8 assays and cell counting. The apoptosis, cell cycle distribution, and ROS were evaluated by flow cytometry. Intracellular iron status was evaluated by atomic absorption spectroscopy and Calcein-AM/2,2'-bipyridyl. The expression of cell cycle and iron metabolism-related genes were analyzed by Western Blot. The result showed that 12 T HiSMF exposure suppressed the proliferation of osteosarcoma cell lines MNNG/HOS, U-2 OS, and MG63 via cell cycle arrest in S and G2/M. Meanwhile, 12 T HiSMF increasing intracellular ROS, and its antitumor effect was reduced by antioxidant. Furthermore, the intracellular total and free iron levels, the expression of FTH1 and DMT1 were increased by 12 HiSMF. The iron chelator (DFO) could reduce the cytotoxicity of 12 T HiSMF on osteosarcoma cells. Moreover, 12 T HiSMF could enhance the cytotoxicity of cisplatin and sorafenib in osteosarcoma cells. In Conclusion, 12 T HiSMF could suppress osteosarcoma cells proliferation via intracellular iron and ROS related cell cycle arrest, and have application potential in osteosarcoma therapy combined with sorafenib and cisplatin.

Iron plays a role in sulfasalazine-induced ferroptosis with autophagic flux blockage in K7M2 osteosarcoma cells.

Osteosarcoma is the most common primary bone malignancy in children and young adults, with a very poor prognosis. It is of great importance to develop targeted therapeutic strategies for osteosarcoma. Sulfasalazine (SAS) is an FDA-approved drug for the treatment of Crohn's disease, rheumatoid arthritis, and inflammatory bowel disease. It acts as an inhibitor of cystine/glutamate system, which is important for cellular glutathione synthesis and maintenance of GPx4 activity. Nowadays, SAS has been repurposed as an antitumor drug for inducing ferroptosis in cancers. This study aimed to uncover the role of iron in SAS-induced ferroptotic cell death in K7M2 osteosarcoma cells. Herein, SAS led to an iron-dependent cell death mode in K7M2 cells, accompanied with decreased antioxidant defense and increased production of cytosolic and lipid reactive oxygen species. Results also showed that iron supplement with ferric ammonium citrate (FAC) or ferrous ammonium sulfate (FAS) exacerbated the declined cell viability of SAS-treated K7M2 cells, while in the case of iron depletion, it weakened such suppression. Furthermore, iron promoted SAS-induced alterations on cell cycle, cytoskeleton, mitochondria morphology and function, and redox system. Iron also induced the dysfunction of autophagic activity in SAS-treated K7M2 cells. In conclusion, our study uncovered the essential role of iron in SAS's effects on K7M2 cells and provided the potential combined therapy of inhibition on antioxidant defense and an increase in oxidative potential, which further disturbed the redox status in tumor cells.

Evaluating the biological safety on mice at 16 T static magnetic field with 700 MHz radio-frequency electromagnetic field.

OBJECTIVES: This study evaluated the associated biological effects of radio-frequency (RF) exposure at 16 T magnetic resonance imaging (MRI) on mice health. MATERIAL AND METHODS: A total of 48 healthy 8-week-old male C57BL/6 mice were investigated. A 16 T high static magnetic field (HiSMF) was generated by a superconducting magnet, and a radiofrequency (RF) electromagnetic field for hydrogen resonance at 16 T (700 MHz) was transmitted via a homemade RF system. The mice were exposed inside the 16 T HiSMF with the 700 MHz RF field for 60 min, and the body weight, organ coefficients, histomorphology of major organs, and blood indices were analyzed for the basal state of the mice on day 0 and day 14. The Heat Shock Protein 70 (HSP70), cyclooxygenase 2 (COX2), and interleukin- 6 (IL-6) were used to evaluate the thermal effects on the brain. Locomotor activity, the open field test, tail suspension test, forced swimming test, and grip strength test were used to assess the behavioral characteristics of the mice. RESULTS: The 16 T HiSMF with 700 MHz RF electromagnetic field exposure had no significant effects on body weight, organ coefficients, or histomorphology of major organs in the mice. On day 0, the expressions of HSP70 and COX2 in the brain were increased by 16 T HiSMF with 700 MHz RF electromagnetic field exposure. However, the expression of HSP70, COX2, and IL-6 had no significant difference compared with the sham group on day 14. Compared with the sham groups, the meancorpuscularvolume (MCV) on day 0 and the total protein (TP) on day 14 were increased significantly, whereas the other blood indices did not change significantly. The 16 T HiSMF with 700 MHz RF electromagnetic field exposure caused the mice to briefly circle tightly but had no effect on other behavioral indicators. CONCLUSIONS: In summary, 16 T HiSMF with 700 MHz RF electromagnetic field exposure for 60 min did not have severe effects on mice.