| Static magnetic fields(SMFs)are constant fields,which do not change in intensity or direction over time.All the living beings on the earth originate,evolve and live under natural geomagnetic field(GMF,25-65 ?T).Interplanetary space is a natural hypomagnetic field(Hy MF,<5 ?T),which will pose adverse impacts on many aspects of biological processes.Unfolding the mechanism of the biological responses to the Hy MF is the fundament for developing the countermeasures of the adverse space environmental factors,and has recently become a hot topic in the field of space life sciences.With the wide application of superconducting technology,high SMF(Hi MF,>1 T)can be produced by magnetic resonance imaging and diamagnetic levitation.Besides,due to the widespread use of electricity in the human daily life,humans are more likely to be exposed to moderate SMF(MMF,1 m T-1 T).Taken together,the frequency of exposure to man-made SMFs has increased progressively from Hy MF,MMF to Hi MF.Exposure to various SMFs from natural and man-made sources remains an environmental issue of public concern in consideration of their probable health risks for humans.Many animal studies concerned with health effects have demonstrated that SMFs with moderate intensity can improve bone formation with increased bone mineral density(BMD)and enhance bone healing in numerous circumstances,such as bone surgical invasion,ischemic bones,adjuvant arthritis rats,bone fracture,ovariectomized rats,and bone grafts.As a physical stimulus,the following parameters of SMF should be considered: magnetic induction(ranging from Hy MF to Hi MF),exposure duration,magnetic gradient,and types of biological samples used(animals,cells or molecules).Moreover,almost all the researches focus on SMFs generated by permanent magnets.Because the used cell types,magnetic intensities,and exposure duration are largely heterogeneous,thus it is difficult to draw a definite conclusion that how osteoblast and osteoclast,the key functional cells involved in bone remodeling,respond to SMF? What is the corelation between magnetic intensity and biological effects? What is the possible mechanism? The present research will offer novel findings in the bioelectromagnetic field,provide new mechanism theory about how SMF regulates bone remodeling,and help us better utilize magneto theropy.In order to comprehensively examine the regulatory role of SMF on bone metabolism,Hy MF of about 500 n T(created by magnetic shielding room),MMF of 0.2 T(surrounding a superconducting magnet)and Hi MF of 16 T(generated by a superconducting magnet)were employed to investigate the SMF effects on proliferation and differentiation in osteoblastic MC3T3-E1 cells and pre-osteoclastic RAW264.7 cells.Microstructure and mechanical properties in femur were also investigated in animal study.GMF deprivation(i.e.Hy MF),even Hi MF did not have lethal effects on the growth of osteoblastic MC3T3-E1 cells and pre-osteoclastic RAW264.7 cells.The differentiation of bone cells could be regulated by SMF intensities.For osteoblast,16 T retarded the initial stage of osteogenic differentiation,but accelerated matrix maturation,ultimately enhancing osteoblast differentiation.500 n T and 0.2 T had inhibitory effects.On the contrary,there was a significant promotion in osteoclast differentiation under 500 n T and 0.2 T,while 16 T inhibited the process.These results showed that the intensity that had positive(16 T)or negative(500 n T and 0.2 T)effects on osteoblast differentiation would inversely influence osteoclast differentiation.After male C57BL/6 mice were solely exposed to 500 n T or 0.2 T for 30 days,both microstructure and mechanical properties in femur were not influenced.SMF stimulation alone would not have adverse effects on mice bone health.The present study further examined whether nitric oxide(NO)was involved in the response to SMF on osteoclast formation.Under 16 T,osteoclast formation was markedly decreased with enhanced activity of nitric oxide synthase(NOS),thus producing a high level of NO.When treated with NOS inhibitor NG-Nitro-L-arginine methyl ester(L-NAME),NO production could be inhibited,and osteoclast formation was promoted to GMF-control level in a concentrationdependent manner finally.On the other hand,500 n T and 0.2 T increased osteoclast formation with decreased NOS activity and NO production.When treated with NOS substrate L-Arginine(L-Arg)or NO donor sodium nitroprusside(SNP),NO level in culture medium was obviously elevated,thus inhibiting osteoclast differentiation in a concentration-dependent manner under 500 n T or 0.2 T.Taken together,NO may mediate the regulatory role of SMF on osteoclast formation.The correlation between mineral elements and bone metabolism was also investigated.The results showed that osteoblasts during mineralization accumulated more copper,iron,manganese,magnesium and zinc,indicating that these mineral elements may be involved in regulating osteoblast differentiation.We also found that the effects of SMFs on osteoblast mineralization accompanied by the alteration of mineral elements.The SMFs effects may be associated with regulations of these elements.Based on the above studies,it is indicated that SMF could at cellular level affect behaviors of osteoblast and osteoblast.Certain intensity of SMF could be used as a non-invasive and physical therapy on maintenance of bone health and treatment of bone disorders synergistically.Under Hy MF,osteoblast differentiation was inhibited,while osteoclast activity was promoted.Animal study demonstrated that SMF alone would not pose adverse effects on bone tissue.Furthermore,NO and mineral elements may mediate the SMF effects.These results will contribute to our better understanding of the geomagnetic field's function on the health of human beings,prediction of the potential effects of the hypomagnetic fields of deep space on the health of astronaut,and understanding of the mechanism of SMF as physical therapy on bone disorders. |
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