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Irp2 Knockout Causes Osteoporosis by Inhibition of Bone Remodeling
- Source :
- Calcified tissue international. 104(1)
- Publication Year :
- 2018
-
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.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Iron Overload
Endocrinology, Diabetes and Metabolism
Iron
Osteoporosis
Osteoclasts
030209 endocrinology & metabolism
Bone tissue
Bone resorption
Bone and Bones
Bone remodeling
03 medical and health sciences
0302 clinical medicine
Endocrinology
Osteoclast
Bone Density
Internal medicine
medicine
Cathepsin K
Animals
Orthopedics and Sports Medicine
Iron Regulatory Protein 2
Bone mineral
Mice, Knockout
Osteoblasts
Chemistry
Osteoblast
medicine.disease
medicine.anatomical_structure
030101 anatomy & morphology
Bone Remodeling
Subjects
Details
- ISSN :
- 14320827
- Volume :
- 104
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Calcified tissue international
- Accession number :
- edsair.doi.dedup.....ae6bd6718b93e74e844e921e7909870a