Xiaoyi Guo, Jie Xu, Lin Chen, He Huang, Zewei Gao, Xijia Jiang
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引用次数: 0
Abstract
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.
期刊介绍:
Journal of Investigative Surgery publishes peer-reviewed scientific articles for the advancement of surgery, to the ultimate benefit of patient care and rehabilitation. It is the only journal that encompasses the individual and collaborative efforts of scientists in human and veterinary medicine, dentistry, basic and applied sciences, engineering, and law and ethics. The journal is dedicated to the publication of outstanding articles of interest to the surgical research community.