Ferrostatin-1 inhibits osteoclast differentiation and prevents osteoporosis by suppressing lipid peroxidation
Abstract Background Osteoporosis (OP) is a systemic disease characterized by low bone mass. New progress has been made in the study of OP, such as lipid peroxidation. However, the role of lipid peroxides in osteoclast differentiation is still unclear. Methods Bone marrow macrophages (BMMs) were extr...
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BMC
2025-01-01
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| Series: | Journal of Orthopaedic Surgery and Research |
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| Online Access: | https://doi.org/10.1186/s13018-025-05544-2 |
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| author | Wenbo Xu Shiyan Lv Xiaoyan Wang Chengchao Song Chunyang Xi Jinglong Yan |
| author_facet | Wenbo Xu Shiyan Lv Xiaoyan Wang Chengchao Song Chunyang Xi Jinglong Yan |
| author_sort | Wenbo Xu |
| collection | DOAJ |
| description | Abstract Background Osteoporosis (OP) is a systemic disease characterized by low bone mass. New progress has been made in the study of OP, such as lipid peroxidation. However, the role of lipid peroxides in osteoclast differentiation is still unclear. Methods Bone marrow macrophages (BMMs) were extracted from C57BL/6J mice and induced to differentiate into osteoclasts, which were observed via TRAP staining, Phalloidin staining and bone pit assays. Related substances of lipid peroxidation were detected during osteoclastogenesis. The levels of osteoclastogenesis and lipid peroxides were measured by qRT-PCR, Western Blot and immunofluorescence. Activation of the p38/JNK/MAPK pathway was detected by Western Blot. The capacity for osteogenesis and angiogenesis of cells after treatment with supernatant of BMMs was evaluated. Furthermore, Ferrostatin-1 (Fer-1), from which femur and serum samples were comprehensively evaluated, was used in OVX mice. Results During osteoclastogenesis, the levels of ROS, MDA, ACSL4 and LPCAT3 increased with increasing duration of RANKL stimulation, while there were no significant changes in the levels of GSH or GPX4. Fer-1 inhibited osteoclast differentiation and decreased the level of lipid peroxides. In addition, Fer-1 inhibited osteoclast-related markers by inhibiting the p38/JNK/MAPK pathway. Furthermore, the supernatant of BMMs after Fer-1 treatment promoted osteogenesis and angiogenesis. Finally, Fer-1 successfully alleviated OP in OVX mice by reducing the level of lipid peroxidation in vivo. Conclusion Fer-1 suppresses osteoclast differentiation by reducing lipid peroxidation levels regulated by ACSL4, which is mediated through the p38/JNK/MAPK signaling pathway. Additionally, Fer-1 enhances the coupling between osteogenesis and angiogenesis and has an anti-OP effect in vivo. |
| format | Article |
| id | doaj-art-cee26a6808b44bd09d729f430a88870b |
| institution | Kabale University |
| issn | 1749-799X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj-art-cee26a6808b44bd09d729f430a88870b2025-02-02T12:33:59ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2025-01-0120111510.1186/s13018-025-05544-2Ferrostatin-1 inhibits osteoclast differentiation and prevents osteoporosis by suppressing lipid peroxidationWenbo Xu0Shiyan Lv1Xiaoyan Wang2Chengchao Song3Chunyang Xi4Jinglong Yan5Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Orthopedics, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Orthopedics, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Orthopedics, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Orthopedics, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Orthopedics, The Second Affiliated Hospital of Harbin Medical UniversityAbstract Background Osteoporosis (OP) is a systemic disease characterized by low bone mass. New progress has been made in the study of OP, such as lipid peroxidation. However, the role of lipid peroxides in osteoclast differentiation is still unclear. Methods Bone marrow macrophages (BMMs) were extracted from C57BL/6J mice and induced to differentiate into osteoclasts, which were observed via TRAP staining, Phalloidin staining and bone pit assays. Related substances of lipid peroxidation were detected during osteoclastogenesis. The levels of osteoclastogenesis and lipid peroxides were measured by qRT-PCR, Western Blot and immunofluorescence. Activation of the p38/JNK/MAPK pathway was detected by Western Blot. The capacity for osteogenesis and angiogenesis of cells after treatment with supernatant of BMMs was evaluated. Furthermore, Ferrostatin-1 (Fer-1), from which femur and serum samples were comprehensively evaluated, was used in OVX mice. Results During osteoclastogenesis, the levels of ROS, MDA, ACSL4 and LPCAT3 increased with increasing duration of RANKL stimulation, while there were no significant changes in the levels of GSH or GPX4. Fer-1 inhibited osteoclast differentiation and decreased the level of lipid peroxides. In addition, Fer-1 inhibited osteoclast-related markers by inhibiting the p38/JNK/MAPK pathway. Furthermore, the supernatant of BMMs after Fer-1 treatment promoted osteogenesis and angiogenesis. Finally, Fer-1 successfully alleviated OP in OVX mice by reducing the level of lipid peroxidation in vivo. Conclusion Fer-1 suppresses osteoclast differentiation by reducing lipid peroxidation levels regulated by ACSL4, which is mediated through the p38/JNK/MAPK signaling pathway. Additionally, Fer-1 enhances the coupling between osteogenesis and angiogenesis and has an anti-OP effect in vivo.https://doi.org/10.1186/s13018-025-05544-2Fer-1OsteoporosisOsteoclastLipid peroxidationACSL4 |
| spellingShingle | Wenbo Xu Shiyan Lv Xiaoyan Wang Chengchao Song Chunyang Xi Jinglong Yan Ferrostatin-1 inhibits osteoclast differentiation and prevents osteoporosis by suppressing lipid peroxidation Journal of Orthopaedic Surgery and Research Fer-1 Osteoporosis Osteoclast Lipid peroxidation ACSL4 |
| title | Ferrostatin-1 inhibits osteoclast differentiation and prevents osteoporosis by suppressing lipid peroxidation |
| title_full | Ferrostatin-1 inhibits osteoclast differentiation and prevents osteoporosis by suppressing lipid peroxidation |
| title_fullStr | Ferrostatin-1 inhibits osteoclast differentiation and prevents osteoporosis by suppressing lipid peroxidation |
| title_full_unstemmed | Ferrostatin-1 inhibits osteoclast differentiation and prevents osteoporosis by suppressing lipid peroxidation |
| title_short | Ferrostatin-1 inhibits osteoclast differentiation and prevents osteoporosis by suppressing lipid peroxidation |
| title_sort | ferrostatin 1 inhibits osteoclast differentiation and prevents osteoporosis by suppressing lipid peroxidation |
| topic | Fer-1 Osteoporosis Osteoclast Lipid peroxidation ACSL4 |
| url | https://doi.org/10.1186/s13018-025-05544-2 |
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