Iron Chelation Inhibits Osteoclastic Differentiation In Vitro and in Tg2576 Mouse Model of Alzheimer’s Disease
Jun Peng Guo,Jun Peng Guo,Jun Peng Guo,Jin-Xiu Pan,Lei Xiong,Lei Xiong,Wen Fang Xia,Wen Fang Xia,Shun Cui,Shun Cui,Wen Cheng Xiong,Wen Cheng Xiong +11 more
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TLDR
In vivo and in vitro studies demonstrate a potent inhibition on OC formation and activation in APPswe-expressing BMMs by iron chelation, and reveal a potential therapeutic value of CQ in treating AD-associated osteoporotic deficits.Abstract:
Patients of Alzheimer's disease (AD) frequently have lower bone mineral density and higher rate of hip fracture. Tg2576, a well characterized AD animal model that ubiquitously express Swedish mutant amyloid precursor protein (APPswe), displays not only AD-relevant neuropathology, but also age-dependent bone deficits. However, the underlying mechanisms remain poorly understood. As APP is implicated as a regulator of iron export, and the metal chelation is considered as a potential therapeutic strategy for AD, we examined iron chelation's effect on the osteoporotic deficit in Tg2576 mice. Remarkably, in vivo treatment with iron chelator, clinoquinol (CQ), increased both trabecular and cortical bone-mass, selectively in Tg2576, but not wild type (WT) mice. Further in vitro studies showed that low concentrations of CQ as well as deferoxamine (DFO), another iron chelator, selectively inhibited osteoclast (OC) differentiation, without an obvious effect on osteoblast (OB) differentiation. Intriguingly, both CQ and DFO's inhibitory effect on OC was more potent in bone marrow macrophages (BMMs) from Tg2576 mice than that of wild type controls. The reduction of intracellular iron levels in BMMs by CQ was also more dramatic in APPswe-expressing BMMs. Taken together, these results demonstrate a potent inhibition on OC formation and activation in APPswe-expressing BMMs by iron chelation, and reveal a potential therapeutic value of CQ in treating AD-associated osteoporotic deficits.read more
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Journal ArticleDOI
Influence of Iron on Bone Homeostasis.
TL;DR: Better understanding of this complex process may help the development of novel therapeutic approaches to deal with the pathologic effects of altered iron levels on bone.
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Serum Copper, Zinc, and Iron Levels in Patients with Alzheimer's Disease: A Meta-Analysis of Case-Control Studies.
TL;DR: The results of this meta-analysis provided rigorous statistical support for the association of the serum levels of metals and the risk of AD, suggesting a positive relationship between the serum copper levels and AD risk, and a negative relationshipbetween the serum zinc/iron levels andAD risk.
Journal ArticleDOI
Wnt5a is a key target for the pro-osteogenic effects of iron chelation on osteoblast progenitors
Ulrike Baschant,Martina Rauner,Ekaterina Balaian,Heike Weidner,Antonella Roetto,Uwe Platzbecker,Lorenz C. Hofbauer +6 more
TL;DR: Data demonstrate that Wnt5a is critical for the pro-osteogenic effects of iron chelation using deferoxamine, and confirmed the requirement of Wnt 5a in the deferredoxamine-mediated osteoblast-promoting effects by analyzing the matrix mineralization of WNT5a-deficient cells.
Journal ArticleDOI
Deletion of ferroportin in murine myeloid cells increases iron accumulation and stimulates osteoclastogenesis in vitro and in vivo
Lei Wang,Bin Fang,Toshifumi Fujiwara,Kimberly J. Krager,Akshita Gorantla,Chaoyuan Li,Jian Q. Feng,Michael Jennings,Jian Zhou,Nukhet Aykin-Burns,Haibo Zhao +10 more
TL;DR: It is indicated that FPN-regulated intracellular iron levels are critical for mitochondrial metabolism, osteoclastogenesis, and skeletal homeostasis in mice.
Journal ArticleDOI
Desferrioxamine reduces ultrahigh-molecular-weight polyethylene-induced osteolysis by restraining inflammatory osteoclastogenesis via heme oxygenase-1.
Hui Kang,Yufei Yan,Peng Jia,Kai Yang,Changjun Guo,Hao Chen,Jin Qi,Niandong Qian,Xing Xu,Fei Wang,Changwei Li,Lei Guo,Lianfu Deng +12 more
TL;DR: It is demonstrated for the first time that desferrioxamine (DFO), a powerful iron chelator, could significantly alleviate osteolysis in an ultrahigh-molecular-weight polyethylene (UHMWPE) particles-induced mice calvaria osteolytic model and suggested that DFO might be used as an innovative and safe therapeutic alternative for treating wear particles- induced aseptic loosening.
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