ArticlePloS one2015
Iron Chelation Inhibits Osteoclastic Differentiation In Vitro and in Tg2576 Mouse Model of Alzheimer's Disease.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Inflammatory Bridges: Interconnections Between Alzheimer's Disease and Bone Health.Aging and disease · 2025Review
- The potential link between the development of Alzheimer's disease and osteoporosis.Biogerontology · 2025Review
- Iron and Bone Pathophysiology.Advances in experimental medicine and biology · 2025Review
- Recent Advances in Targeting Transition Metals (Copper, Iron, and Zinc) in Alzheimer's Disease.Molecular neurobiology · 2024Review
- Iron Deficiency and Iron Deficiency Anemia: Potential Risk Factors in Bone Loss.International journal of molecular sciences · 2023Review
- Desferrioxamine alleviates UHMWPE particle-induced osteoclastic osteolysis by inhibiting caspase-1-dependent pyroptosis in osteocytes.Journal of biological engineering · 2022Article
- Article
- Hepcidin contributes to Swedish mutant APP-induced osteoclastogenesis and trabecular bone loss.Bone research · 2021Article
- Picolinic acid, a tryptophan oxidation product, does not impact bone mineral density but increases marrow adiposity.Experimental gerontology · 2020Article
- Influence of Iron on Bone Homeostasis.Pharmaceuticals (Basel, Switzerland) · 2018Review
- Deletion of ferroportin in murine myeloid cells increases iron accumulation and stimulates osteoclastogenesisThe Journal of biological chemistry · 2018Article
- Serum Copper, Zinc, and Iron Levels in Patients with Alzheimer's Disease: A Meta-Analysis of Case-Control Studies.Frontiers in aging neuroscience · 2017Article
- Wnt5a is a key target for the pro-osteogenic effects of iron chelation on osteoblast progenitors.Haematologica · 2016Article
- Desferrioxamine reduces ultrahigh-molecular-weight polyethylene-induced osteolysis by restraining inflammatory osteoclastogenesis via heme oxygenase-1.Cell death & disease · 2016Article
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
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.
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