PTH 1-34 promoted bone formation by regulating iron metabolism in unloading-induced bone loss
PTH 1-34 (teriparatide) is approved by FDA for the treatment of postmenopausal osteoporosis. Iron overload is a major contributing factor for bone loss induced by unloading. Whether iron metabolism is involved in the regulation of PTH 1-34 on unloading-induced osteoporosis has not yet been reported....
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.1048818/full |
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| author | Jingmin Che Jingmin Che Weihao Ren Weihao Ren Weihao Ren Xin Chen Xin Chen Fang Wang Fang Wang Gejing Zhang Gejing Zhang Peng Shang Peng Shang |
| author_facet | Jingmin Che Jingmin Che Weihao Ren Weihao Ren Weihao Ren Xin Chen Xin Chen Fang Wang Fang Wang Gejing Zhang Gejing Zhang Peng Shang Peng Shang |
| author_sort | Jingmin Che |
| collection | DOAJ |
| description | PTH 1-34 (teriparatide) is approved by FDA for the treatment of postmenopausal osteoporosis. Iron overload is a major contributing factor for bone loss induced by unloading. Whether iron metabolism is involved in the regulation of PTH 1-34 on unloading-induced osteoporosis has not yet been reported. Here, we found that PTH 1-34 attenuated bone loss in unloading mice. PTH 1-34 regulated the disturbance of iron metabolism in unloading mice by activating Nrf2 and further promoting hepcidin expression in the liver. In addition, the Nrf2 inhibitor selectively blocked hepcidin expression in the liver of unloading mice, which neutralized the inhibitory effect of PTH 1-34 on bone loss and the recovery of iron metabolism in unloading mice. Finally, we found that PTH 1-34 promoted the differentiation and inhibited apoptosis of osteoblasts by regulating iron metabolism and maintaining redox balance under unloading conditions. Our results suggested that PTH 1-34 promoted bone formation by regulating iron metabolism under unloading conditions. |
| first_indexed | 2024-04-10T18:05:06Z |
| format | Article |
| id | doaj.art-8fa62e81a75444469c5f9f72de2bd37e |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-10T18:05:06Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-8fa62e81a75444469c5f9f72de2bd37e2023-02-02T13:20:55ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-02-011310.3389/fendo.2022.10488181048818PTH 1-34 promoted bone formation by regulating iron metabolism in unloading-induced bone lossJingmin Che0Jingmin Che1Weihao Ren2Weihao Ren3Weihao Ren4Xin Chen5Xin Chen6Fang Wang7Fang Wang8Gejing Zhang9Gejing Zhang10Peng Shang11Peng Shang12Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, Guangdong, ChinaShaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People’s Hospital, Xi’an, ChinaResearch & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, Guangdong, ChinaSchool of Life Sciences, Northwestern Polytechnical University, Xi’an, Shaanxi, ChinaKey Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi’an, Shaanxi, ChinaSchool of Life Sciences, Northwestern Polytechnical University, Xi’an, Shaanxi, ChinaKey Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi’an, Shaanxi, ChinaSchool of Life Sciences, Northwestern Polytechnical University, Xi’an, Shaanxi, ChinaKey Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi’an, Shaanxi, ChinaSchool of Life Sciences, Northwestern Polytechnical University, Xi’an, Shaanxi, ChinaKey Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi’an, Shaanxi, ChinaResearch & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, Guangdong, ChinaKey Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi’an, Shaanxi, ChinaPTH 1-34 (teriparatide) is approved by FDA for the treatment of postmenopausal osteoporosis. Iron overload is a major contributing factor for bone loss induced by unloading. Whether iron metabolism is involved in the regulation of PTH 1-34 on unloading-induced osteoporosis has not yet been reported. Here, we found that PTH 1-34 attenuated bone loss in unloading mice. PTH 1-34 regulated the disturbance of iron metabolism in unloading mice by activating Nrf2 and further promoting hepcidin expression in the liver. In addition, the Nrf2 inhibitor selectively blocked hepcidin expression in the liver of unloading mice, which neutralized the inhibitory effect of PTH 1-34 on bone loss and the recovery of iron metabolism in unloading mice. Finally, we found that PTH 1-34 promoted the differentiation and inhibited apoptosis of osteoblasts by regulating iron metabolism and maintaining redox balance under unloading conditions. Our results suggested that PTH 1-34 promoted bone formation by regulating iron metabolism under unloading conditions.https://www.frontiersin.org/articles/10.3389/fendo.2022.1048818/fullunloadingPTH 1-34bone formationiron metabolismNRF2 |
| spellingShingle | Jingmin Che Jingmin Che Weihao Ren Weihao Ren Weihao Ren Xin Chen Xin Chen Fang Wang Fang Wang Gejing Zhang Gejing Zhang Peng Shang Peng Shang PTH 1-34 promoted bone formation by regulating iron metabolism in unloading-induced bone loss Frontiers in Endocrinology unloading PTH 1-34 bone formation iron metabolism NRF2 |
| title | PTH 1-34 promoted bone formation by regulating iron metabolism in unloading-induced bone loss |
| title_full | PTH 1-34 promoted bone formation by regulating iron metabolism in unloading-induced bone loss |
| title_fullStr | PTH 1-34 promoted bone formation by regulating iron metabolism in unloading-induced bone loss |
| title_full_unstemmed | PTH 1-34 promoted bone formation by regulating iron metabolism in unloading-induced bone loss |
| title_short | PTH 1-34 promoted bone formation by regulating iron metabolism in unloading-induced bone loss |
| title_sort | pth 1 34 promoted bone formation by regulating iron metabolism in unloading induced bone loss |
| topic | unloading PTH 1-34 bone formation iron metabolism NRF2 |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.1048818/full |
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