title: Hepcidin inhibition on the effect of osteogenesis in zebrafish.
abstract: Iron overload, as a risk factor for osteoporosis, can result in the up-regulation of Hepcidin, and Hepcidin knockout mice display defects in their bone microarchitecture. However, the molecular and genetic mechanisms underlying Hepcidin deficiency-derived bone loss remain unclear. Here, we show that hepcidin knockdown in zebrafish using morpholinos leads to iron overload. Furthermore, a mineralization delay is observed in osteoblast cells in hepcidin morphants, and these defects could be partially restored with microinjection of hepcidin mRNA. Quantitative real-time PCR analyses revealed the osteoblast-specific genes alp, runx2a, runx2b, and sp7 in morphants are down-regulated. Furthermore, we confirmed qRT-PCR results by in situ hybridization and found down-regulated genes related to osteoblast function in hepcidin morphants. Most importantly, we revealed that hepcidin was capable of removing whole-body iron which facilitated larval recovery from the reductions in bone formation and osteogenesis induced by iron overload.
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou 215004, China; Department of Orthopedics, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi 214000, China; Osteoporosis Diagnosis and Treatment Technology, Institute of Soochow University, 1055 Sanxiang Road, Suzhou 215004, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, OR, USA.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou 215004, China; Osteoporosis Diagnosis and Treatment Technology, Institute of Soochow University, 1055 Sanxiang Road, Suzhou 215004, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi 214000, China. Electronic address: jiangyu314@sohu.com.
authors.forename: Guoxing
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou 215004, China; Osteoporosis Diagnosis and Treatment Technology, Institute of Soochow University, 1055 Sanxiang Road, Suzhou 215004, China. Electronic address: xuyoujia@medmail.com.cn.
authors.forename: You-Jia
authors.initials: YJ
authors.lastname: Xu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D064451:Hepcidins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D060172:Morpholinos / Q000235:genetics; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis; D010802:Phylogeny; D012333:RNA, Messenger / Q000235:genetics; D015027:Zebrafish / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D064451:Hepcidins; D060172:Morpholinos; D012333:RNA, Messenger; D029961:Zebrafish Proteins; C000618866:hamp protein, zebrafish; D007501:Iron
keywords: Hepcidin; Iron overload; Morpholino; Zebrafish