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Disorder of iron metabolism inhibits the recovery of unloading-induced bone loss in hypomagnetic field

Xue Y1,2,3Yang J2,4,3Luo J1,2,3Ren L2,3Shen Y1,2,3Dong D1,2,3Fang Y5Hu L5Liu M5Liao Z5Li J5Fang Z5Shang P1,3.

J Bone Miner Res. 2019 Dec 27. doi: 10.1002/jbmr.3949. [Epub ahead of print]

 

 

Abstract

Exposure of humans and animals to microgravity in spaceflight results in variously deleterious effects on bone health. In addition to microgravity, the hypomagnetic field (HyMF) also is an extreme environment in space, such as on the Moon and Mars, magnetic intensity is far weaker than the geomagnetic field (GMF) on the earth. Recently, we demonstrated that HyMF promoted additional bone loss in hindlimb unloading-induced bone loss, and the underlying mechanism probably involved in the increase of body iron storage. Numerous studies have indicated that bone loss induced by mechanical unloading can be largely restored after skeletal reloading in GMF condition. However, it is unknown whether this bone deficit can return to a healthy state under HyMF condition. Therefore, the purpose of this study is to examine the effects of HyMF on the recovery of microgravity-induced bone loss, and illustrates the changes of body iron storage in this process. Our results demonstrated that there was lower bone mineral content (BMC) in the HyMF reloading group compared to the GMF reloading group. Reloaded mice in the HyMF condition had a worse microstructure of femur than in the GMF condition. Femoral mechanical properties, including the elastic modulus, stiffness, and ultimate stress were poorer and toughness was higher in the HyMF group compared with the GMF group. Simultaneously, more iron content in serum, the tibia, liver and spleen were found under HyMF reloading than GMF reloading. The iron chelator deferoxamine mesylate (DFO) decreased the iron content in the bone, liver and spleen, and significantly relieved unloading-induced bone loss under HyMF reloading. These results showed that HyMF inhibits the recovery of microgravity-induced bone loss, probably by suppressing elevated iron levels return to physiological level.