Vitamin K2 inhibits PGE2-mediated osteoblast ferroptosis by upregulation of CBR1 via the Nrf2/Keap1 pathway
Abstract Osteoporosis is increasingly attracting attention. Studies have indicated a correlation between vitamin K2 levels and bone mass, but the specific mechanisms remain unclear. Therefore, this study aims to further elucidate the specific molecular mechanisms and related target proteins. We foun...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08564-0 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849342542250770432 |
|---|---|
| author | Lin Tao Hongyang Li Jinpeng Wang Qichang Liu Wenhai Cao Yue Zhu |
| author_facet | Lin Tao Hongyang Li Jinpeng Wang Qichang Liu Wenhai Cao Yue Zhu |
| author_sort | Lin Tao |
| collection | DOAJ |
| description | Abstract Osteoporosis is increasingly attracting attention. Studies have indicated a correlation between vitamin K2 levels and bone mass, but the specific mechanisms remain unclear. Therefore, this study aims to further elucidate the specific molecular mechanisms and related target proteins. We found that serum vitamin K2 level in osteoporosis women was significantly lower than that in normal women. Animal experiments confirmed the anti-osteoporotic effects of vitamin K2. The mechanism and target of vitamin K2 therapy for osteoporosis was investigated through metabolomics and transcriptomics sequencing. Molecular docking was employed to identify downstream target proteins of vitamin K2, while EMSA and ChIP-qPCR were used to explore the specific molecular mechanisms. The results indicate that vitamin K2 promotes bone formation. Additionally, vitamin K2 may bind to the downstream target protein Nrf2 and inhibit Keap1-mediated ubiquitination, and Nrf2 has been shown to up-regulate CBR1 to inhibit osteoblast ferroptosis caused by the inflammatory factor PGE2. In summary, our study demonstrates that Vitamin K2 attenuates bone loss by inhibiting osteoblast ferroptosis, highlighting its therapeutic potential for osteoporosis. These findings advance our understanding of Vitamin K2-mediated osteoprotective effects and facilitate the identification of novel drug targets for osteoporosis treatment. |
| format | Article |
| id | doaj-art-ace9f43664c549b4a2fa0ee220abe1d2 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-ace9f43664c549b4a2fa0ee220abe1d22025-08-20T03:43:21ZengNature PortfolioCommunications Biology2399-36422025-07-018111610.1038/s42003-025-08564-0Vitamin K2 inhibits PGE2-mediated osteoblast ferroptosis by upregulation of CBR1 via the Nrf2/Keap1 pathwayLin Tao0Hongyang Li1Jinpeng Wang2Qichang Liu3Wenhai Cao4Yue Zhu5Department of Orthopedics, First Hospital of China Medical UniversityDepartment of Orthopedics, First Hospital of China Medical UniversityDepartment of Orthopedics, First Hospital of China Medical UniversityDepartment of Orthopedics, First Hospital of China Medical UniversityDepartment of Orthopedics, First Hospital of China Medical UniversityDepartment of Orthopedics, First Hospital of China Medical UniversityAbstract Osteoporosis is increasingly attracting attention. Studies have indicated a correlation between vitamin K2 levels and bone mass, but the specific mechanisms remain unclear. Therefore, this study aims to further elucidate the specific molecular mechanisms and related target proteins. We found that serum vitamin K2 level in osteoporosis women was significantly lower than that in normal women. Animal experiments confirmed the anti-osteoporotic effects of vitamin K2. The mechanism and target of vitamin K2 therapy for osteoporosis was investigated through metabolomics and transcriptomics sequencing. Molecular docking was employed to identify downstream target proteins of vitamin K2, while EMSA and ChIP-qPCR were used to explore the specific molecular mechanisms. The results indicate that vitamin K2 promotes bone formation. Additionally, vitamin K2 may bind to the downstream target protein Nrf2 and inhibit Keap1-mediated ubiquitination, and Nrf2 has been shown to up-regulate CBR1 to inhibit osteoblast ferroptosis caused by the inflammatory factor PGE2. In summary, our study demonstrates that Vitamin K2 attenuates bone loss by inhibiting osteoblast ferroptosis, highlighting its therapeutic potential for osteoporosis. These findings advance our understanding of Vitamin K2-mediated osteoprotective effects and facilitate the identification of novel drug targets for osteoporosis treatment.https://doi.org/10.1038/s42003-025-08564-0 |
| spellingShingle | Lin Tao Hongyang Li Jinpeng Wang Qichang Liu Wenhai Cao Yue Zhu Vitamin K2 inhibits PGE2-mediated osteoblast ferroptosis by upregulation of CBR1 via the Nrf2/Keap1 pathway Communications Biology |
| title | Vitamin K2 inhibits PGE2-mediated osteoblast ferroptosis by upregulation of CBR1 via the Nrf2/Keap1 pathway |
| title_full | Vitamin K2 inhibits PGE2-mediated osteoblast ferroptosis by upregulation of CBR1 via the Nrf2/Keap1 pathway |
| title_fullStr | Vitamin K2 inhibits PGE2-mediated osteoblast ferroptosis by upregulation of CBR1 via the Nrf2/Keap1 pathway |
| title_full_unstemmed | Vitamin K2 inhibits PGE2-mediated osteoblast ferroptosis by upregulation of CBR1 via the Nrf2/Keap1 pathway |
| title_short | Vitamin K2 inhibits PGE2-mediated osteoblast ferroptosis by upregulation of CBR1 via the Nrf2/Keap1 pathway |
| title_sort | vitamin k2 inhibits pge2 mediated osteoblast ferroptosis by upregulation of cbr1 via the nrf2 keap1 pathway |
| url | https://doi.org/10.1038/s42003-025-08564-0 |
| work_keys_str_mv | AT lintao vitamink2inhibitspge2mediatedosteoblastferroptosisbyupregulationofcbr1viathenrf2keap1pathway AT hongyangli vitamink2inhibitspge2mediatedosteoblastferroptosisbyupregulationofcbr1viathenrf2keap1pathway AT jinpengwang vitamink2inhibitspge2mediatedosteoblastferroptosisbyupregulationofcbr1viathenrf2keap1pathway AT qichangliu vitamink2inhibitspge2mediatedosteoblastferroptosisbyupregulationofcbr1viathenrf2keap1pathway AT wenhaicao vitamink2inhibitspge2mediatedosteoblastferroptosisbyupregulationofcbr1viathenrf2keap1pathway AT yuezhu vitamink2inhibitspge2mediatedosteoblastferroptosisbyupregulationofcbr1viathenrf2keap1pathway |