Iron overload increases osteoclastogenesis and aggravates the effects of ovariectomy on bone mass
Iron overload increases osteoclastogenesis and aggravates the effects of ovariectomy on bone mass
复制标题
铁超载会增加破骨细胞生成并加剧卵巢切除术对骨量的影响
DOI：
10.1530/joe-14-0657
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发表时间：
2015-09-01
影响因子：
4
通讯作者：
Xu Youjia
中科院分区：
文献类型：
--
作者：
Wang Xiao;Fei Beibei;Xu Youjia
绝经后骨质疏松症是一种与雌激素缺乏有关的代谢性疾病。大量的研究结果表明铁的积累与绝经后骨质疏松症之间存在正相关性。虽然以前的研究结果表明，雌激素或铁单独对骨代谢有影响，但它们的联合作用还没有得到很好的定义。使用体内小鼠模型，我们发现，骨质受到影响最小的过量铁在雌激素的存在。一旦雌激素的来源被删除（卵巢切除术），铁积累显着降低骨量。这些影响伴随着氧化应激水平的波动。为了确定这些作用是否与骨形成或骨吸收有关，将原代成骨细胞（OB）、RAW 264.7细胞和骨髓来源的巨噬细胞用于体外实验。我们发现铁的积累确实抑制了OBs的活性，但是雌激素对这种抑制作用的影响很小。相反，铁促进破骨细胞的分化，通过产生活性氧。雌激素，一种强大的活性氧清除剂，抑制破骨细胞的这种作用。我们的数据提供了直接的证据表明，铁只在没有雌激素的情况下影响骨量。雌激素对铁诱导的骨质减少的抑制作用与骨吸收而不是骨形成特别相关。
Postmenopausal osteoporosis is a metabolic disease associated with estrogen deficiency. The results of numerous studies have revealed the positive correlation between iron accumulation and postmenopausal osteoporotic status. Although the results of previous studies have indicated that estrogen or iron alone have an effect on bone metabolism, their combined effects are not well defined. Using an in vivo mouse model, we found that bone mass was minimally affected by an excess of iron in the presence of estrogen. Once the source of estrogen was removed ( ovariectomy), iron accumulation significantly decreased bone mass. These effects were accompanied by fluctuations in the level of oxidative stress. To determine whether these effects were related to bone formation or bone resorption, primary osteoblasts (OBs), RAW264.7 cells, and bone-marrow-derived macrophages were used for in vitro experiments. We found that iron accumulation did inhibit the activity of OBs. However, estrogen had little effect on this inhibition. In contrast, iron promoted osteoclast differentiation through the production of reactive oxygen species. Estrogen, a powerful reactive oxygen scavenger, suppressed this effect in osteoclasts. Our data provided direct evidence that iron affected the bone mass only in the absence of estrogen. The inhibitory effect of estrogen on iron-induced osteopenia was particularly relevant to bone resorption rather than bone formation.