Excess iron inhibits osteoblast metabolism

Toxicol Lett. 2009 Dec 15;191(2-3):211-5. doi: 10.1016/j.toxlet.2009.08.023. Epub 2009 Sep 6.


Hemochromatosis is an iron overload disorder associated with osteopenia and osteoporosis. To learn more about the effects of iron on bone cells, we examined the effects of ferric ion on the proliferation, differentiation, and mineralization of two types of cultured osteoblasts, the cell line MC3T3-E1 and rat calvarial osteoblast-like (ROB) cells. We used ferric ammonium citrate (FAC) as a donor of ferric ion, and FAC inhibited the proliferation of MC3T3-E1 cells in a dose-dependent manner. FAC (0.1-1 microg/ml) inhibited indices of osteoblast differentiation, such as the expression of type I collagen (mRNA and protein), the activity of alkaline phosphatase, and the deposition of calcium by osteoblasts. These results suggest that iron overload might give rise to osteoporosis by inhibiting osteoblast proliferation and differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone and Bones / cytology
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism
  • Calcification, Physiologic / drug effects
  • Calcium / metabolism
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Citric Acid / pharmacology
  • Collagen Type I / metabolism
  • Iron / toxicity*
  • Mice
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism*
  • Quaternary Ammonium Compounds / pharmacology
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skull / drug effects
  • Skull / metabolism


  • Collagen Type I
  • Quaternary Ammonium Compounds
  • Citric Acid
  • ammonium citrate
  • Iron
  • Alkaline Phosphatase
  • Calcium