Ferric ion could facilitate osteoclast differentiation and bone resorption through the production of reactive oxygen species

The Second Affiliated Hospital of Soochow University, Department of Orthopaedics, China, Jiangsu Province, 1055 Sanxiang Road, Suzhou, Jiangsu, China.
Journal of Orthopaedic Research (Impact Factor: 2.99). 11/2012; 30(11):1843-52. DOI: 10.1002/jor.22133
Source: PubMed


Iron overload is widely regarded as a risk factor for osteoporosis. It has been demonstrated that iron can inhibit osteoblast differentiation. However, the effects of iron on osteoclast differentiation and bone resorption remain controversial. In this study, we found that ferric ion promoted Receptor Activator of Nuclear Factor κ B Ligand (RANKL)-induced osteoclast (OC) formation in both RAW264.7 cells and bone marrow-derived macrophages (BMMs), and this effect was accompanied by elevated levels of reactive oxygen species (ROS) and oxidative stress. Moreover, this effect was attenuated by the administration of antioxidant N-acetyl-L-cysteine (NAC). Therefore, we conclude that ferric ion can promote osteoclast differentiation and bone resorption through the production of ROS. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1843-1852, 2012.

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    • "Iron is a trace element that has important functions in vivo[63]. In the skeletal system, both excess and insufficient iron can reduce bone mass[64]–[66]. In vitro, iron can even inhibit the growth of hydroxyapatite crystals[67]. "
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    • "In other words, excess iron promoted the activity of osteoclasts, and then elevated bone resorption process, with resultant loss of bone strength. In terms of the molecular mechanisms, previous studies have demonstrated that intracellular iron retention would cause massive production of reactive oxygen species (ROS) through Fenton reaction (Fridovich, 1978; Galaris and Pantopoulos, 2008; Halliwell and Gutteridge, 1990), and ROS is postulated to be an instigator of bone resorption (Jia et al., 2012). Jia and colleagues demonstrated that iron overload could promote osteoclast differentiation and bone resorption through stimulation of ROS (Ishii et al., 2009; Yamasaki and Hagiwara, 2009). "
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