Iron overload-induced ferroptosis of osteoblasts inhibits osteogenesis and promotes osteoporosis: An in vitro and in vivo study

作者全名："Jiang, Zengxin; Wang, Hao; Qi, Guobin; Jiang, Chang; Chen, Kangning; Yan, Zuoqin"

作者地址："[Jiang, Zengxin; Qi, Guobin; Jiang, Chang; Chen, Kangning; Yan, Zuoqin] Fudan Univ, Zhongshan Hosp, Dept Orthoped Surg, Shanghai, Peoples R China; [Wang, Hao] Chongqing Med Univ, Affiliated Hosp 2, Dept Orthoped, Chongqing, Peoples R China"

通信作者："Yan, ZQ (通讯作者)，Fudan Univ, Zhongshan Hosp, 180 Feng Lin Rd, Shanghai 200032, Peoples R China."

来源：IUBMB LIFE

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000809385400001

JCR分区：Q3

影响因子：4.6

年份：2022

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：ferroptosis; iron overload; osteoblast; osteoporosis

摘要："Growing evidence indicates that iron overload is an independent risk factor for osteoporosis. However, the mechanisms are not fully understood. The purpose of our study was to determine whether iron overload could lead to ferroptosis in osteoblasts and to explore whether ferroptosis of osteoblasts is involved in iron overload-induced osteoporosis in vitro and in vivo. Ferric ammonium citrate was used to mimic iron overload conditions, while deferoxamine and ferrostatin-1 were used to inhibit ferroptosis of MC3T3-E1 cells in vitro. The ferroptosis, osteogenic differentiation and mineralization of MC3T3-E1 cells were assessed in vitro. A mouse iron overload model was established using iron dextran. Immunohistochemical analysis was performed to determine ferroptosis of osteoblasts in vivo. Enzyme-linked immunosorbent assays and calcein-alizarin red S labelling were used to assess new bone formation. Dual x-ray absorptiometry, micro-computed tomography and histopathological analysis were conducted to evaluate osteoporosis. The results showed that iron overload reduced cell viability, superoxide dismutase and glutathione levels, increased reactive oxygen species generation, lipid peroxidation, malondialdehyde levels and ferroptosis-related protein expression, and induced ultrastructural changes in mitochondria. Iron overload could also inhibit osteogenic differentiation and mineralization in vitro. Inhibiting ferroptosis reversed the changes described above. Iron overload inhibited osteogenesis, promoted the ferroptosis of osteoblasts and induced osteoporosis in vivo, which could also be improved by deferoxamine and ferrostatin-1. These results demonstrate that ferroptosis of osteoblasts plays a crucial role in iron overload-induced osteoporosis. Maintaining iron homeostasis and targeting ferroptosis of osteoblasts might be potential measures of treating or preventing iron overload-induced osteoporosis."

基金机构："National Natural Science Foundation of China [81871742, 82172413]; Shanghai Hospital Development Center [SHDC2020CR3075B]"

基金资助正文："National Natural Science Foundation of China, Grant/Award Numbers: 81871742, 82172413; Shanghai Hospital Development Center, Grant/Award Number: SHDC2020CR3075B"