Iron accumulation induced by hepcidin1 knockout accelerates the progression of aging osteoporosis
Abstract Objective Iron accumulation is associated with osteoporosis. This study aims to explore the effect of chronic iron accumulation induced by hepcidin1 deficiency on aging osteoporosis. Methods Iron accumulation in hepcidin1 knockout aging mice was assessed by atomic absorption spectroscopy an...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Journal of Orthopaedic Surgery and Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13018-024-04535-z |
| _version_ | 1827382042713653248 |
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| author | Lu-lin Liu Zhong-rui Liu Lu-jun Cao Jun Wang San-ming Huang Shui-gen Hu Yi-zhong Yang Dong-sheng Li Wei-wei Cao Qing-bao Zeng Sheng Huang Qiong Wu Jian-hua Xiao Wu-yang Liu Yao-sheng Xiao |
| author_facet | Lu-lin Liu Zhong-rui Liu Lu-jun Cao Jun Wang San-ming Huang Shui-gen Hu Yi-zhong Yang Dong-sheng Li Wei-wei Cao Qing-bao Zeng Sheng Huang Qiong Wu Jian-hua Xiao Wu-yang Liu Yao-sheng Xiao |
| author_sort | Lu-lin Liu |
| collection | DOAJ |
| description | Abstract Objective Iron accumulation is associated with osteoporosis. This study aims to explore the effect of chronic iron accumulation induced by hepcidin1 deficiency on aging osteoporosis. Methods Iron accumulation in hepcidin1 knockout aging mice was assessed by atomic absorption spectroscopy and Perl’s staining. Bone microarchitecture was observed using Micro-CT. Hepcidin, ferritin, oxidative stress, and markers of bone turnover in serum were detected by enzyme-linked immunosorbent assay. Bone formation and resorption markers were measured by real-time quantitative PCR. Cell aging was induced by D-galactose treatment. CCK-8, flow cytometry, EdU assays, and Alizarin red staining were performed to reveal the role of hepcidin1 knockout in cell model. Iron Colorimetric Assay Kit and western blot were applied to detect iron and ferritin levels in cells, respectively. Results In hepcidin1-knockout mice, the ferritin and iron contents in liver and tibia were significantly increased. Iron accumulation induced by hepcidin1 knockout caused a phenotype of low bone mass and deteriorated bone microarchitecture. Osteogenic marker was decreased and osteoclast marker was increased in mice, accompanied by increased oxidative stress level. The mRNA expression levels of osteoclast differentiation markers (RANKL, Mmp9, OPG, Trap, and CTSK) were up-regulated, while bone formation markers (OCN, ALP, Runx2, SP7, and Col-1) were down-regulated in model group, compared to wild type mice. In vitro, hepcidin1 knockdown inhibited proliferation and osteogenic differentiation, while promoted apoptosis, with increased levels of iron and ferritin. Conclusion Iron accumulation induced by hepcidin1 deficiency aggravates the progression of aging osteoporosis via inhibiting osteogenesis and promoting osteoclast genesis. |
| first_indexed | 2024-03-08T14:13:47Z |
| format | Article |
| id | doaj.art-091f294769d9491eb425525b75e7fd46 |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-03-08T14:13:47Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-091f294769d9491eb425525b75e7fd462024-01-14T12:30:13ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2024-01-0119111210.1186/s13018-024-04535-zIron accumulation induced by hepcidin1 knockout accelerates the progression of aging osteoporosisLu-lin Liu0Zhong-rui Liu1Lu-jun Cao2Jun Wang3San-ming Huang4Shui-gen Hu5Yi-zhong Yang6Dong-sheng Li7Wei-wei Cao8Qing-bao Zeng9Sheng Huang10Qiong Wu11Jian-hua Xiao12Wu-yang Liu13Yao-sheng Xiao14Department of Orthopedics, The First Affiliated Hospital of Gannan Medical UniversityDepartment of Orthopedics, The First Affiliated Hospital of Gannan Medical UniversityDepartment of Orthopedics, The People’s Hospital of Ningdu CountyDepartment of Orthopedics, The People’s Hospital of Ningdu CountyDepartment of Orthopedics, The People’s Hospital of Ningdu CountyDepartment of Orthopedics, The People’s Hospital of Ningdu CountyDepartment of Orthopedics, The People’s Hospital of Ningdu CountyDepartment of Orthopedics, The People’s Hospital of Ningdu CountyDepartment of Orthopedics, The People’s Hospital of Ningdu CountyDepartment of Orthopedics, The People’s Hospital of Ningdu CountyDepartment of Orthopedics, The People’s Hospital of Ningdu CountyDepartment of Orthopedics, The People’s Hospital of Ningdu CountyDepartment of Orthopedics, The First Affiliated Hospital of Gannan Medical UniversityDepartment of Orthopedics, The First Affiliated Hospital of Gannan Medical UniversityDepartment of Orthopedics, The First Affiliated Hospital of Gannan Medical UniversityAbstract Objective Iron accumulation is associated with osteoporosis. This study aims to explore the effect of chronic iron accumulation induced by hepcidin1 deficiency on aging osteoporosis. Methods Iron accumulation in hepcidin1 knockout aging mice was assessed by atomic absorption spectroscopy and Perl’s staining. Bone microarchitecture was observed using Micro-CT. Hepcidin, ferritin, oxidative stress, and markers of bone turnover in serum were detected by enzyme-linked immunosorbent assay. Bone formation and resorption markers were measured by real-time quantitative PCR. Cell aging was induced by D-galactose treatment. CCK-8, flow cytometry, EdU assays, and Alizarin red staining were performed to reveal the role of hepcidin1 knockout in cell model. Iron Colorimetric Assay Kit and western blot were applied to detect iron and ferritin levels in cells, respectively. Results In hepcidin1-knockout mice, the ferritin and iron contents in liver and tibia were significantly increased. Iron accumulation induced by hepcidin1 knockout caused a phenotype of low bone mass and deteriorated bone microarchitecture. Osteogenic marker was decreased and osteoclast marker was increased in mice, accompanied by increased oxidative stress level. The mRNA expression levels of osteoclast differentiation markers (RANKL, Mmp9, OPG, Trap, and CTSK) were up-regulated, while bone formation markers (OCN, ALP, Runx2, SP7, and Col-1) were down-regulated in model group, compared to wild type mice. In vitro, hepcidin1 knockdown inhibited proliferation and osteogenic differentiation, while promoted apoptosis, with increased levels of iron and ferritin. Conclusion Iron accumulation induced by hepcidin1 deficiency aggravates the progression of aging osteoporosis via inhibiting osteogenesis and promoting osteoclast genesis.https://doi.org/10.1186/s13018-024-04535-zIronHepcidinOsteoporosisAged mice |
| spellingShingle | Lu-lin Liu Zhong-rui Liu Lu-jun Cao Jun Wang San-ming Huang Shui-gen Hu Yi-zhong Yang Dong-sheng Li Wei-wei Cao Qing-bao Zeng Sheng Huang Qiong Wu Jian-hua Xiao Wu-yang Liu Yao-sheng Xiao Iron accumulation induced by hepcidin1 knockout accelerates the progression of aging osteoporosis Journal of Orthopaedic Surgery and Research Iron Hepcidin Osteoporosis Aged mice |
| title | Iron accumulation induced by hepcidin1 knockout accelerates the progression of aging osteoporosis |
| title_full | Iron accumulation induced by hepcidin1 knockout accelerates the progression of aging osteoporosis |
| title_fullStr | Iron accumulation induced by hepcidin1 knockout accelerates the progression of aging osteoporosis |
| title_full_unstemmed | Iron accumulation induced by hepcidin1 knockout accelerates the progression of aging osteoporosis |
| title_short | Iron accumulation induced by hepcidin1 knockout accelerates the progression of aging osteoporosis |
| title_sort | iron accumulation induced by hepcidin1 knockout accelerates the progression of aging osteoporosis |
| topic | Iron Hepcidin Osteoporosis Aged mice |
| url | https://doi.org/10.1186/s13018-024-04535-z |
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