title: Iron overload increases osteoclastogenesis and aggravates the effects of ovariectomy on bone mass.
abstract: Postmenopausal osteoporosis is a metabolic disease associated with estrogen deficiency. The results of numerous studies have revealed the positive correlation between iron accumulation and postmenopausal osteoporotic status. Although the results of previous studies have indicated that estrogen or iron alone have an effect on bone metabolism, their combined effects are not well defined. Using an in vivo mouse model, we found that bone mass was minimally affected by an excess of iron in the presence of estrogen. Once the source of estrogen was removed (ovariectomy), iron accumulation significantly decreased bone mass. These effects were accompanied by fluctuations in the level of oxidative stress. To determine whether these effects were related to bone formation or bone resorption, primary osteoblasts (OBs), RAW264.7 cells, and bone-marrow-derived macrophages were used for in vitro experiments. We found that iron accumulation did inhibit the activity of OBs. However, estrogen had little effect on this inhibition. In contrast, iron promoted osteoclast differentiation through the production of reactive oxygen species. Estrogen, a powerful reactive oxygen scavenger, suppressed this effect in osteoclasts. Our data provided direct evidence that iron affected the bone mass only in the absence of estrogen. The inhibitory effect of estrogen on iron-induced osteopenia was particularly relevant to bone resorption rather than bone formation.
authors.affiliation: Departments of OrthopaedicsGynaecologyThe Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, 215004 Suzhou, ChinaDepartment of Orthopaedic Research InstitutionSoochow University, 215004 Suzhou, ChinaDepartment of MedicineNew York University School of Medicine, 10016 New York, New York, USA.
authors.forename: Wang
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Departments of OrthopaedicsGynaecologyThe Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, 215004 Suzhou, ChinaDepartment of Orthopaedic Research InstitutionSoochow University, 215004 Suzhou, ChinaDepartment of MedicineNew York University School of Medicine, 10016 New York, New York, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Beibei
authors.affiliation: Departments of OrthopaedicsGynaecologyThe Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, 215004 Suzhou, ChinaDepartment of Orthopaedic Research InstitutionSoochow University, 215004 Suzhou, ChinaDepartment of MedicineNew York University School of Medicine, 10016 New York, New York, USA.
authors.forename: Shen
authors.initials: S
authors.lastname: Guangsi
authors.affiliation: Departments of OrthopaedicsGynaecologyThe Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, 215004 Suzhou, ChinaDepartment of Orthopaedic Research InstitutionSoochow University, 215004 Suzhou, ChinaDepartment of MedicineNew York University School of Medicine, 10016 New York, New York, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Yu
authors.affiliation: Departments of OrthopaedicsGynaecologyThe Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, 215004 Suzhou, ChinaDepartment of Orthopaedic Research InstitutionSoochow University, 215004 Suzhou, ChinaDepartment of MedicineNew York University School of Medicine, 10016 New York, New York, USA.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Departments of OrthopaedicsGynaecologyThe Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, 215004 Suzhou, ChinaDepartment of Orthopaedic Research InstitutionSoochow University, 215004 Suzhou, ChinaDepartment of MedicineNew York University School of Medicine, 10016 New York, New York, USA.
authors.forename: Huang
authors.initials: H
authors.lastname: Xi
authors.affiliation: Departments of OrthopaedicsGynaecologyThe Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, 215004 Suzhou, ChinaDepartment of Orthopaedic Research InstitutionSoochow University, 215004 Suzhou, ChinaDepartment of MedicineNew York University School of Medicine, 10016 New York, New York, USA xuyoujia@medmail.com.cn.
authors.forename: Xu
authors.initials: X
authors.lastname: Youjia
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005290:Ferric Compounds / Q000494:pharmacology; D019190:Iron Overload / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D010052:Ovariectomy; D018384:Oxidative Stress / Q000502:physiology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D005290:Ferric Compounds; D000644:Quaternary Ammonium Compounds; D017382:Reactive Oxygen Species; D004958:Estradiol; C013531:ferric ammonium citrate
keywords: estrogen; iron; osteoclasts; osteoporosis; oxidative stress