Background: Women transitioned to postmenopausal status experience a corresponding gain in iron stores. Recently clinical researches have observed increased serum ferritin level in postmenopausal women, and ferritin level was negatively correlated with bone mineral density.
Purpose: To explore the mechanism of iron-induced osteopenia in mouse model.
Methods: Briefly, in this study, we established an iron accumulation mouse model with ovariectomy. Primary osteoclasts and osteoblasts were extracted for this research. Biomarkers of bone metabolism and cell signaling pathways were measured.
Results: We found that bone mass changed later than ferritin and decreased gradually following overiectomy. We also observed higher levels of bone resorption and oxidative stress when iron was administered. When stimulated with iron, primary osteoclasts derived from bone marrow-derived macrophages (BMMs) underwent differentiation and numerous reactive oxygen species (ROS) were generated. Further, we found that iron activated the JNK, ERK and NF-κB signaling pathways in vivo. In vitro, we found that only NF-κB signaling was stimulated by iron and that suppression of this pathway blocked osteoclast differentiation. To determine whether these effects were related to ROS, osteoclasts were treated with H2O2. We found that ROS stimulated osteoclast activity, and that this effect was reversed upon NF-κB suppression.
Conclusions: These data suggest that ROS might be a downstream factor of iron and regulated NF-κB signaling in osteoclasts in mouse model.
Keywords: Iron; NF-κB; Osteoclast; ROS.
Copyright © 2018. Published by Elsevier Inc.