title: Therapeutic effect of deferoxamine on iron overload-induced inhibition of osteogenesis in a zebrafish model.
abstract: Osteoporosis results from an imbalance in bone remodeling, in which osteoclastic bone resorption exceeds osteoblastic bone formation. Iron has recently been recognized as an independent risk factor for osteoporosis. Reportedly, excess iron could promote osteoclast differentiation and bone resorption through the production of reactive oxygen species (ROS). We evaluated the effect of iron on osteoblast differentiation and bone formation in zebrafish and further investigated the potential benefits of deferoxamine (DFO), a powerful iron chelator, in iron-overloaded zebrafish. The zebrafish model of iron overload described in this study demonstrated an apparent inhibition of bone formation, accompanied by decreased expression of osteoblast-specific genes (runx2a, runx2b, osteocalcin, osteopontin, ALP, and collagen type I). The negative effect of iron on osteoblastic activity and bone formation could be attributed to increased ROS generation and oxidative stress. Most importantly, we revealed that DFO was capable of removing whole-body iron and attenuating oxidative stress in iron-overloaded larval zebrafish, which facilitated larval recovery from the reductions in bone formation and osteogenesis induced by iron overload.
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Yan
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Bo
authors.forename: Guang-Fei
authors.initials: GF
authors.lastname: Li
authors.forename: Han
authors.initials: H
authors.lastname: Wang
authors.forename: You-Jia
authors.initials: YJ
authors.lastname: Xu
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology*; D004195:Disease Models, Animal; D019190:Iron Overload / Q000188:drug therapy*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015027:Zebrafish
chemical_list: D017382:Reactive Oxygen Species; D003676:Deferoxamine