Department of Orthopaedicsthe Second Affiliated Hospital of Soochow University, Suzhou, China.
Emergency DepartmentZhongshan Hospital Affiliated to Fudan University, Shanghai, China.
J Mol Endocrinol. 2018 May;60(4):297-306. doi: 10.1530/JME-17-0301. Epub 2018 Mar 21.
Postmenopausal osteoporosis is a global health issue. Although a lack of estrogen is considered the major reason for postmenopausal osteoporosis, other factors might also contribute the etiology of the disease. In previous reports, we and others proposed that iron accumulation after menopause accelerates osteoporosis, and here, we genetically modified the expression of an endogenous hormone, hepcidin, to modulate iron status in a mouse model. Our results show that hepcidin levels negatively correlate with bone loss in both knockout and overexpression (with ovariectomy) murine models. In addition, iron overload enhances reactive oxygen species (ROS) activity and attenuates the functions of primary osteoblasts, while iron depletion could reverse this phenomenon through inhibiting the functions of primary osteoclasts. Therefore, our results provide more evidence of the 'iron accumulation' hypothesis, which suggests that high iron levels are risk factors for osteoporosis, and the 'Huang's hypothesis' that hepcidin is a potential drug target for the prevention of postmenopausal osteoporosis.
绝经后骨质疏松症是一个全球性的健康问题。尽管雌激素缺乏被认为是绝经后骨质疏松症的主要原因，但其他因素也可能导致疾病的发生。在之前的报告中，我们和其他人提出绝经后铁的积累会加速骨质疏松症，在这里，我们通过基因修饰一种内源性激素——铁调素的表达，在小鼠模型中调节铁的状态。我们的结果表明，铁调素水平与敲除和过表达（卵巢切除）小鼠模型中的骨丢失呈负相关。此外，铁过载会增强活性氧（ROS）的活性，减弱原代成骨细胞的功能，而铁耗竭则可以通过抑制原代破骨细胞的功能来逆转这种现象。因此，我们的结果为“铁积累”假说提供了更多的证据，该假说表明高铁水平是骨质疏松症的危险因素，以及“Huang 假说”，即铁调素是预防绝经后骨质疏松症的潜在药物靶点。
