Effects of mouse hepcidin 1 treatment on osteoclast differentiation and intracellular iron concentration

Hepcidin is a key player in the regulation of mammalian iron homeostasis. Because iron overload may be one of the causes of osteoporosis, hepcidin may have therapeutic potential for osteoporosis patients. However, the effects of hepcidin on bone metabolism are not fully clear. We recently found that hepcidin can increase intracellular iron and calcium levels and promote mineralization in osteoblasts. The present study was designed to evaluate the effects of hepcidin on osteoclasts. Our results showed that mouse hepcidin 1 (MH1) can increase the number of TRAP-positive MNCs concomitant in both bone marrow-derived macrophages (BMMs) and RAW264.7 cells and upregulate mRNA levels of TRAP, Cathepsin K, and MMP-9 and increase TRAP-5b protein secretion in RAW264.7 cells. Moreover, MH1 can downregulate the level of FPN1 protein and increase intracellular iron in RAW 264.7 cells. Therefore, we conclude that MH1 can significantly facilitate osteoclast differentiation in vitro. The mechanism behind accelerated differentiation may be associated with increased levels of intracellular iron. These findings may facilitate understanding of the effects of hepcidin on bone metabolism.