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01-01-2019 | Original Research

Irp2 Knockout Causes Osteoporosis by Inhibition of Bone Remodeling

Authors: Yaru Zhou, Yu Yang, Yan Liu, Hengrui Chang, Kuanzhi Liu, Xiaojuan Zhang, Yanzhong Chang

Published in: Calcified Tissue International | Issue 1/2019

Abstract

It has been found that iron disorder may lead to osteoporosis. However, the mechanism has been little explored. In the present study, we try to investigate the effects of iron disorder on bone metabolism using Irp2 knockout (Irp2^−/−) mice. Female Irp2^−/− mice were used in this study. Bone mineral density (BMD) was measured by Micro-CT. Serum markers for bone turnover were measured by enzyme-linked immunosorbent assay. Content of iron was measured in bone and liver tissue, and Vitamin D 25-hydroxylase (CYP2R1) content was measured in liver tissue. Relative gene expression involved in iron export and uptake, and some genes involved in activities of osteoblast and osteoclast were all measured by real-time PCR and western blot. Compared to wild-type mice, Irp2^−/− mice exhibited reduced BMD, bone iron deficiency, and hepatic iron overload. Serum levels of 25(OH)D₃ and markers for bone formation such as bone alkaline phosphatase (Balp), bone-gla-protein (BGP), and type I collagen alpha1 chain (Col I α₁) were decreased, while markers for bone resorption including cathepsin K (Ctsk) and tartrate-resistant acid phosphatase (Trap) were all significantly increased. Hepatic CYP2R1 level was decreased in Irp2^−/− mice compared with wild-type control mice. Compared to wild-type C57BL6 control mice, the expression of genes involved in osteoblast activity such as Balp, BGP, and Col I α₁ were all significantly decreased in bone tissue, while genes for osteoclast activity such as Ctsk and Trap were all markedly increased in Irp2^−/− mice at mRNA level. Genes involved in iron storage, uptake, and exporting were also measured in bone tissue. Posttranscriptionally decreased ferritin (FTL), ferroportin 1 (FPN1), and increased transferrin receptor 1 (TfR1) gene expressions have been unexpectedly found in bone tissue of Irp2^−/− mice. Irp2^−/− mice exhibit reduced bone iron content and osteoporosis. Decreased circulating 25(OH)D₃ levels promoted activity of osteoclast, while impaired activity of osteoblast may contribute to pathogenesis of osteoporosis. And, reduced bone iron content may not be totally caused by TfR1-dependent pathways.

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Title: Irp2 Knockout Causes Osteoporosis by Inhibition of Bone Remodeling
Authors: Yaru Zhou
Yu Yang
Yan Liu
Hengrui Chang
Kuanzhi Liu
Xiaojuan Zhang
Yanzhong Chang
Publication date: 01-01-2019
Publisher: Springer US
Published in: Calcified Tissue International / Issue 1/2019
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-018-0469-2

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