Functional Study of the circRNA_0006393/miR-375/IGFBP4 Axis in Fracture Healing Associated with Male Idiopathic Osteoporosis
Background CircRNA_0006393 was reported to promote osteogenesis in glucocorticoid-induced osteoporosis, but its role in male idiopathic osteoporosis (MIO) has not been revealed.Aim To explore circRNA_0006393’s role in MIO.Methods Dual-luciferase reporter assay was performed to notarize the direct co...
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Taylor & Francis Group
2025-12-01
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| Series: | Journal of Investigative Surgery |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/08941939.2025.2535522 |
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| author | Xiaoyi Guo Jie Xu Lin Chen He Huang Zewei Gao Xijia Jiang |
| author_facet | Xiaoyi Guo Jie Xu Lin Chen He Huang Zewei Gao Xijia Jiang |
| author_sort | Xiaoyi Guo |
| collection | DOAJ |
| description | Background CircRNA_0006393 was reported to promote osteogenesis in glucocorticoid-induced osteoporosis, but its role in male idiopathic osteoporosis (MIO) has not been revealed.Aim To explore circRNA_0006393’s role in MIO.Methods Dual-luciferase reporter assay was performed to notarize the direct connection among circRNA_0006393, miR-375 and IGFBP4. Their value as biomarkers of MIO was confirmed by the ROC curve. The osteogenic induction was measured by detecting the ALP activity/expression and OCN/RUNX2 expression. The osteoclastic induction was evaluated by detecting TRAP activity and bone resorption capacity. The concentration of Fe2+, GSH, and ROS was detected to evaluate ferroptosis.Results MiR-375 was overexpressed in MIO patients, while circRNA_000639 and IGFBP4 presented low expression. CircRNA_0006393 promoted IGFBP4 expression by sponging miR-375. The AUC of circulating circRNA_0006393, miR-375, IGFBP4, or their combination in distinguishing unhealing and healing individuals with MIO-related fracture was 0.840, 0.851, 0.743, 0.960, respectively. CircRNA_0006393 reduced the ferroptosis process by regulating miR-375/IGFBP4. Iron overload inhibited the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSC) and promoted the osteoclastic differentiation of bone marrow-derived macrophage cells (BMMC).Conclusion CircRNA_000639 inhibited ferroptosis by regulating the miR-375/IGFBP4 axis, thereby promoting osteogenesis and hindering osteoclastic differentiation, and they are the biomarkers for MIO-related fracture healing. |
| format | Article |
| id | doaj-art-03fa9f77c3764d5fbab889e338b716bd |
| institution | DOAJ |
| issn | 0894-1939 1521-0553 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Investigative Surgery |
| spelling | doaj-art-03fa9f77c3764d5fbab889e338b716bd2025-08-20T02:46:21ZengTaylor & Francis GroupJournal of Investigative Surgery0894-19391521-05532025-12-0138110.1080/08941939.2025.2535522Functional Study of the circRNA_0006393/miR-375/IGFBP4 Axis in Fracture Healing Associated with Male Idiopathic OsteoporosisXiaoyi Guo0Jie Xu1Lin Chen2He Huang3Zewei Gao4Xijia Jiang5Sports Medicine Department, Wuxi Hospital of Traditional Chinese Medicine, Wuxi, ChinaDepartment of Orthopedics, Changzhou Second People’s Hospital, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, ChinaDepartment of Orthopedics I, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, ChinaEmergency Department, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Orthopedics I, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Orthopedics, Changzhou Second People’s Hospital, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, ChinaBackground CircRNA_0006393 was reported to promote osteogenesis in glucocorticoid-induced osteoporosis, but its role in male idiopathic osteoporosis (MIO) has not been revealed.Aim To explore circRNA_0006393’s role in MIO.Methods Dual-luciferase reporter assay was performed to notarize the direct connection among circRNA_0006393, miR-375 and IGFBP4. Their value as biomarkers of MIO was confirmed by the ROC curve. The osteogenic induction was measured by detecting the ALP activity/expression and OCN/RUNX2 expression. The osteoclastic induction was evaluated by detecting TRAP activity and bone resorption capacity. The concentration of Fe2+, GSH, and ROS was detected to evaluate ferroptosis.Results MiR-375 was overexpressed in MIO patients, while circRNA_000639 and IGFBP4 presented low expression. CircRNA_0006393 promoted IGFBP4 expression by sponging miR-375. The AUC of circulating circRNA_0006393, miR-375, IGFBP4, or their combination in distinguishing unhealing and healing individuals with MIO-related fracture was 0.840, 0.851, 0.743, 0.960, respectively. CircRNA_0006393 reduced the ferroptosis process by regulating miR-375/IGFBP4. Iron overload inhibited the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSC) and promoted the osteoclastic differentiation of bone marrow-derived macrophage cells (BMMC).Conclusion CircRNA_000639 inhibited ferroptosis by regulating the miR-375/IGFBP4 axis, thereby promoting osteogenesis and hindering osteoclastic differentiation, and they are the biomarkers for MIO-related fracture healing.https://www.tandfonline.com/doi/10.1080/08941939.2025.2535522male idiopathic osteoporosiscircRNA_0006393miR-375IGFBP4ferroptosis |
| spellingShingle | Xiaoyi Guo Jie Xu Lin Chen He Huang Zewei Gao Xijia Jiang Functional Study of the circRNA_0006393/miR-375/IGFBP4 Axis in Fracture Healing Associated with Male Idiopathic Osteoporosis Journal of Investigative Surgery male idiopathic osteoporosis circRNA_0006393 miR-375 IGFBP4 ferroptosis |
| title | Functional Study of the circRNA_0006393/miR-375/IGFBP4 Axis in Fracture Healing Associated with Male Idiopathic Osteoporosis |
| title_full | Functional Study of the circRNA_0006393/miR-375/IGFBP4 Axis in Fracture Healing Associated with Male Idiopathic Osteoporosis |
| title_fullStr | Functional Study of the circRNA_0006393/miR-375/IGFBP4 Axis in Fracture Healing Associated with Male Idiopathic Osteoporosis |
| title_full_unstemmed | Functional Study of the circRNA_0006393/miR-375/IGFBP4 Axis in Fracture Healing Associated with Male Idiopathic Osteoporosis |
| title_short | Functional Study of the circRNA_0006393/miR-375/IGFBP4 Axis in Fracture Healing Associated with Male Idiopathic Osteoporosis |
| title_sort | functional study of the circrna 0006393 mir 375 igfbp4 axis in fracture healing associated with male idiopathic osteoporosis |
| topic | male idiopathic osteoporosis circRNA_0006393 miR-375 IGFBP4 ferroptosis |
| url | https://www.tandfonline.com/doi/10.1080/08941939.2025.2535522 |
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