title: Hepcidin1 knockout mice display defects in bone microarchitecture and changes of bone formation markers.
abstract: Iron accumulation is a risk factor of osteoporosis; mechanisms leading to iron-related bone loss are not fully determined. We sought to better understand the effect of chronic iron accumulation on bone over the life span in a mouse model. Hepcidin1 knockout (Hepc1(-/-)) male mice and their littermate control wild type (WT) mice at 7 months old were used in this study. Serum iron and ferritin as well as iron contents in liver and femur were significantly increased in Hepc1(-/-) mice compared to WT mice. We found that Hepc1(-/-) mice had a phenotype of low bone mass and alteration of the bone microarchitecture, most likely caused by a decreased osteoblastic activity. Cell culture studies indicated that chronic iron accumulation decreased bone formation, probably by affecting bone morphogenetic protein signaling.
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Suzhou, 215004, China.
authors.forename: Guang Si
authors.initials: GS
authors.lastname: Shen
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.forename: Jing Long
authors.initials: JL
authors.lastname: Jian
authors.forename: Guo Yang
authors.initials: GY
authors.lastname: Zhao
authors.forename: Lu Lin
authors.initials: LL
authors.lastname: Liu
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
authors.forename: You Jia
authors.initials: YJ
authors.lastname: Xu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015519:Bone Density / Q000502:physiology; D016723:Bone Remodeling / Q000502:physiology; D001842:Bone and Bones / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D004797:Enzyme-Linked Immunosorbent Assay; D005293:Ferritins / Q000032:analysis / Q000378:metabolism; D064451:Hepcidins / Q000235:genetics / Q000378:metabolism*; D007501:Iron / Q000032:analysis / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010012:Osteogenesis / Q000502:physiology*; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; C579599:Hamp protein, mouse; D064451:Hepcidins; D005293:Ferritins; D007501:Iron