Department of Orthopaedics, Second Affiliated Hospital of Soochow University, 215004 Suzhou, China.
Department of Oncology, First Affiliated Hospital of Soochow University, 215006 Suzhou, China.
Metabolism. 2018 Jun;83:167-176. doi: 10.1016/j.metabol.2018.01.005. Epub 2018 Mar 13.
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.
To explore the mechanism of iron-induced osteopenia in mouse model.
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.
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 HO. We found that ROS stimulated osteoclast activity, and that this effect was reversed upon NF-κB suppression.
These data suggest that ROS might be a downstream factor of iron and regulated NF-κB signaling in osteoclasts in mouse model.
女性进入绝经后状态会相应地增加铁储存。最近的临床研究观察到绝经后女性血清铁蛋白水平升高，而铁蛋白水平与骨密度呈负相关。
探索铁诱导小鼠模型骨质疏松的机制。
简而言之，在这项研究中，我们建立了去卵巢的铁积累小鼠模型。为此研究提取了原代破骨细胞和成骨细胞。测量了骨代谢生物标志物和细胞信号通路。
我们发现骨量的变化晚于铁蛋白，并且在去卵巢后逐渐减少。当给予铁时，我们还观察到更高水平的骨吸收和氧化应激。当用铁刺激时，源自骨髓来源的巨噬细胞（BMM）的原代破骨细胞发生分化并产生大量活性氧（ROS）。此外，我们发现铁在体内激活了 JNK、ERK 和 NF-κB 信号通路。在体外，我们发现只有 NF-κB 信号通路被铁刺激，而抑制该通路可阻断破骨细胞分化。为了确定这些效应是否与 ROS 有关，用 HO 处理破骨细胞。我们发现 ROS 刺激破骨细胞活性，而 NF-κB 抑制可逆转这种作用。
这些数据表明，ROS 可能是铁的下游因子，并调节了小鼠模型中破骨细胞的 NF-κB 信号。
