Iron chelation inhibits osteoclastic differentiation in vitro and in Tg2576 mouse model of Alzheimer's disease

Jun Peng Guo, Jin Xiu Pan, Lei Xiong, Wen Fang Xia, Shun Cui, Wen Cheng Xiong

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article number0139395
JournalPloS one
Volume10
Issue number11
DOIs
StatePublished - Nov 1 2015

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chelation
Alzheimer disease
Chelation
Alzheimer Disease
Bone
Iron
animal models
iron
Macrophages
bone marrow
osteoclasts
macrophages
Osteoclasts
Bone Marrow
Chelating Agents
chelating agents
mice
deferoxamine
hip fractures
bones

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Iron chelation inhibits osteoclastic differentiation in vitro and in Tg2576 mouse model of Alzheimer's disease. / Guo, Jun Peng; Pan, Jin Xiu; Xiong, Lei; Xia, Wen Fang; Cui, Shun; Xiong, Wen Cheng.

In: PloS one, Vol. 10, No. 11, 0139395, 01.11.2015.

Research output: Contribution to journalArticle

Guo, Jun Peng ; Pan, Jin Xiu ; Xiong, Lei ; Xia, Wen Fang ; Cui, Shun ; Xiong, Wen Cheng. / Iron chelation inhibits osteoclastic differentiation in vitro and in Tg2576 mouse model of Alzheimer's disease. In: PloS one. 2015 ; Vol. 10, No. 11.
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