Overload of ferric ammonium citrate triggers MAPK pathways by producing high level of reactive oxygen species and induces apoptosis of human hFOB1.19 osteoblast cells

AIM：To investigate the role of reative oxygen species (ROS) generated by iron overload in activating the mitogen-activated protein kinase (MAPK) pathways and apoptosis. METHODS：Cultured human osteoblast cell line hFOB1.19 was treated with ferric ammonium citrate (FAC) at concentrations of 0~500 μmoL/L. The proliferation of hFOB1.19 cells was analyzed by MTT assay. Apoptosis was detected by flow cytometry with Annexin V/PI staining. The expression levels of p-ERK, p-JNK and p-p38 were determined by Western blotting 24 h after treatment with FAC. RESULTS：After treated with FAC, the cell proliferation was inhibited. The early apoptosis and total cell death were significantly increased. The levels of ROS were increased to (35.73±2.52)%, (62.89±4.24)% and (76.06±3.55)% with the increasing doses of FAC treatmen,respectively. The expression levels of p-ERK, p-JNK and p-p38 were also remarkably elevated in FAC groups. CONCLUSION：Iron overload increases intracellular ROS level, thus triggering the MAPK pathways and inducing apoptosis of human hFOB1.19 osteoblast cells.