Melanoma bone metastasis-induced osteocyte ferroptosis via the HIF1α-HMOX1 axis
Abstract Osteocytes are the main cells in mineralized bone tissue. Elevated osteocyte apoptosis has been observed in lytic bone lesions of patients with multiple myeloma. However, their precise contribution to bone metastasis remains unclear. Here, we investigated the pathogenic mechanisms driving m...
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| Format: | Article |
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Nature Publishing Group
2025-01-01
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| Series: | Bone Research |
| Online Access: | https://doi.org/10.1038/s41413-024-00384-y |
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| author | Yewei Jia Rui Li Yixuan Li Katerina Kachler Xianyi Meng Andreas Gießl Yi Qin Fulin Zhang Ning Liu Darja Andreev Georg Schett Aline Bozec |
| author_facet | Yewei Jia Rui Li Yixuan Li Katerina Kachler Xianyi Meng Andreas Gießl Yi Qin Fulin Zhang Ning Liu Darja Andreev Georg Schett Aline Bozec |
| author_sort | Yewei Jia |
| collection | DOAJ |
| description | Abstract Osteocytes are the main cells in mineralized bone tissue. Elevated osteocyte apoptosis has been observed in lytic bone lesions of patients with multiple myeloma. However, their precise contribution to bone metastasis remains unclear. Here, we investigated the pathogenic mechanisms driving melanoma-induced osteocyte death. Both in vivo models and in vitro assays were combined with untargeted RNA sequencing approaches to explore the pathways governing melanoma-induced osteocyte death. We could show that ferroptosis is the primary mechanism behind osteocyte death in the context of melanoma bone metastasis. HMOX1 was identified as a crucial regulatory factor in this process, directly involved in inducing ferroptosis and affecting osteocyte viability. We uncover a non-canonical pathway that involves excessive autophagy-mediated ferritin degradation, highlighting the complex relationship between autophagy and ferroptosis in melanoma-induced osteocyte death. In addition, HIF1α pathway was shown as an upstream regulator, providing a potential target for modulating HMOX1 expression and influencing autophagy-dependent ferroptosis. In conclusion, our study provides insight into the pathogenic mechanisms of osteocyte death induced by melanoma bone metastasis, with a specific focus on ferroptosis and its regulation. This would enhance our comprehension of melanoma-induced osteocyte death. |
| format | Article |
| id | doaj-art-9e43ab230f534a51a247471ca106591a |
| institution | Kabale University |
| issn | 2095-6231 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Bone Research |
| spelling | doaj-art-9e43ab230f534a51a247471ca106591a2025-01-19T12:13:41ZengNature Publishing GroupBone Research2095-62312025-01-0113111910.1038/s41413-024-00384-yMelanoma bone metastasis-induced osteocyte ferroptosis via the HIF1α-HMOX1 axisYewei Jia0Rui Li1Yixuan Li2Katerina Kachler3Xianyi Meng4Andreas Gießl5Yi Qin6Fulin Zhang7Ning Liu8Darja Andreev9Georg Schett10Aline Bozec11Department of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum ErlangenDepartment of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum ErlangenDepartment of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum ErlangenDepartment of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum ErlangenDepartment of Opthalmology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum ErlangenDepartment of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum ErlangenDepartment of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum ErlangenDepartment of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum ErlangenDepartment of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum ErlangenDepartment of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum ErlangenDepartment of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum ErlangenAbstract Osteocytes are the main cells in mineralized bone tissue. Elevated osteocyte apoptosis has been observed in lytic bone lesions of patients with multiple myeloma. However, their precise contribution to bone metastasis remains unclear. Here, we investigated the pathogenic mechanisms driving melanoma-induced osteocyte death. Both in vivo models and in vitro assays were combined with untargeted RNA sequencing approaches to explore the pathways governing melanoma-induced osteocyte death. We could show that ferroptosis is the primary mechanism behind osteocyte death in the context of melanoma bone metastasis. HMOX1 was identified as a crucial regulatory factor in this process, directly involved in inducing ferroptosis and affecting osteocyte viability. We uncover a non-canonical pathway that involves excessive autophagy-mediated ferritin degradation, highlighting the complex relationship between autophagy and ferroptosis in melanoma-induced osteocyte death. In addition, HIF1α pathway was shown as an upstream regulator, providing a potential target for modulating HMOX1 expression and influencing autophagy-dependent ferroptosis. In conclusion, our study provides insight into the pathogenic mechanisms of osteocyte death induced by melanoma bone metastasis, with a specific focus on ferroptosis and its regulation. This would enhance our comprehension of melanoma-induced osteocyte death.https://doi.org/10.1038/s41413-024-00384-y |
| spellingShingle | Yewei Jia Rui Li Yixuan Li Katerina Kachler Xianyi Meng Andreas Gießl Yi Qin Fulin Zhang Ning Liu Darja Andreev Georg Schett Aline Bozec Melanoma bone metastasis-induced osteocyte ferroptosis via the HIF1α-HMOX1 axis Bone Research |
| title | Melanoma bone metastasis-induced osteocyte ferroptosis via the HIF1α-HMOX1 axis |
| title_full | Melanoma bone metastasis-induced osteocyte ferroptosis via the HIF1α-HMOX1 axis |
| title_fullStr | Melanoma bone metastasis-induced osteocyte ferroptosis via the HIF1α-HMOX1 axis |
| title_full_unstemmed | Melanoma bone metastasis-induced osteocyte ferroptosis via the HIF1α-HMOX1 axis |
| title_short | Melanoma bone metastasis-induced osteocyte ferroptosis via the HIF1α-HMOX1 axis |
| title_sort | melanoma bone metastasis induced osteocyte ferroptosis via the hif1α hmox1 axis |
| url | https://doi.org/10.1038/s41413-024-00384-y |
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