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

J Orthop Res. 2012 Nov;30(11):1843-52. doi: 10.1002/jor.22133. Epub 2012 May 8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine
  • Animals
  • Bone Resorption / metabolism*
  • Cell Differentiation*
  • Cell Line
  • Ferric Compounds
  • Glutathione / metabolism
  • Iron / metabolism*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Osteoclasts / cytology*
  • Oxidative Stress
  • Quaternary Ammonium Compounds
  • RANK Ligand / metabolism
  • Reactive Oxygen Species / metabolism*

Substances

  • Ferric Compounds
  • Quaternary Ammonium Compounds
  • RANK Ligand
  • Reactive Oxygen Species
  • Tnfsf11 protein, mouse
  • Iron
  • Glutathione
  • ferric ammonium citrate
  • Acetylcysteine