Hepcidin contributes to Swedish mutant APP-induced osteoclastogenesis and trabecular bone loss.
Hepcidin contributes to Swedish mutant APP-induced osteoclastogenesis and trabecular bone loss.
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DOI：
10.1038/s41413-021-00146-0
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发表时间：
2021-06-09
期刊：
影响因子：
12.7
通讯作者：
Xiong WC
中科院分区：
文献类型：
--
作者：
Guo HH;Xiong L;Pan JX;Lee D;Liu K;Ren X;Wang B;Yang X;Cui S;Mei L;Xiong WC
Patients with Alzheimer’s disease (AD) often have lower bone mass than healthy individuals. However, the mechanisms underlying this change remain elusive. Previously, we found that Tg2576 mice, an AD animal model that ubiquitously expresses Swedish mutant amyloid precursor protein (APPswe), shows osteoporotic changes, reduced bone formation, and increased bone resorption. To understand how bone deficits develop in Tg2576 mice, we used a multiplex antibody array to screen for serum proteins that are altered in Tg2576 mice and identified hepcidin, a master regulator of iron homeostasis. We further investigated hepcidin’s function in bone homeostasis and found that hepcidin levels were increased not only in the serum but also in the liver, muscle, and osteoblast (OB) lineage cells in Tg2576 mice at both the mRNA and protein levels. We then generated mice selectively expressing hepcidin in hepatocytes or OB lineage cells, which showed trabecular bone loss and increased osteoclast (OC)-mediated bone resorption. Further cell studies suggested that hepcidin increased OC precursor proliferation and differentiation by downregulating ferroportin (FPN) expression and increasing intracellular iron levels. In OB lineage cells, APPswe enhanced hepcidin expression by inducing ER stress and increasing OC formation, in part through hepcidin. Together, these results suggest that increased hepcidin expression in hepatocytes and OB lineage cells in Tg2576 mice contributes to enhanced osteoclastogenesis and trabecular bone loss, identifying the hepcidin-FPN-iron axis as a potential therapeutic target to prevent AD-associated bone loss.
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影响因子：
5.6
作者：
Chang, Yuhan;Hsiao, Yi-min;Chen, Mei-Feng
通讯作者：
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影响因子：
6.2
作者：
Cui, Shun;Xiong, Fei;Hong, Yan;Jung, Ji-Ung;Li, Xing-Sheng;Liu, Jian-Zhong;Yan, Riqiang;Mei, Lin;Feng, Xu;Xiong, Wen-Cheng
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Xiong, Wen-Cheng
影响因子：
4.1
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Yang X
影响因子：
20.3
作者：
Armitage, Andrew E.;Eddowes, Lucy A.;Drakesmith, Hal
通讯作者：
Drakesmith, Hal
DOI：
10.1006/bbrc.2001.5747
发表时间：
2001-10-19
影响因子：
3.1
作者：
Basu, S;Michaëlsson, K;Melhus, H
通讯作者：
Melhus, H