Functional Study of the circRNA_0006393/miR-375/IGFBP4 Axis in Fracture Healing Associated with Male Idiopathic Osteoporosis.

IF 3.5 4区 医学 Q2 SURGERY
Journal of Investigative Surgery Pub Date : 2025-12-01 Epub Date: 2025-07-29 DOI:10.1080/08941939.2025.2535522
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.

circRNA_0006393/miR-375/IGFBP4轴在男性特发性骨质疏松症相关骨折愈合中的功能研究
背景:据报道CircRNA_0006393在糖皮质激素诱导的骨质疏松症中促进骨生成,但其在男性特发性骨质疏松症(MIO)中的作用尚未揭示。目的:探讨circRNA_0006393在MIO中的作用。方法:采用双荧光素酶报告基因法验证circRNA_0006393、miR-375和IGFBP4之间的直接联系。ROC曲线证实了它们作为MIO生物标志物的价值。通过检测ALP活性/表达和OCN/RUNX2表达来检测成骨诱导作用。通过检测TRAP活性和骨吸收能力来评估破骨细胞诱导作用。检测Fe2+、GSH、ROS浓度评价铁下垂。结果:MiR-375在MIO患者中过表达,circRNA_000639和IGFBP4低表达。CircRNA_0006393通过海绵miR-375促进IGFBP4的表达。循环circRNA_0006393、miR-375、IGFBP4或其组合在区分心肌梗死相关骨折未愈合和愈合个体中的AUC分别为0.840、0.851、0.743、0.960。CircRNA_0006393通过调节miR-375/IGFBP4减少铁下垂过程。铁超载抑制骨髓间充质干细胞(BMSC)的成骨分化,促进骨髓源性巨噬细胞(BMMC)的破骨分化。结论:CircRNA_000639通过调控miR-375/IGFBP4轴抑制铁下沉,从而促进成骨,阻碍破骨细胞分化,是io相关骨折愈合的生物标志物。
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来源期刊
CiteScore
4.20
自引率
0.00%
发文量
114
审稿时长
6-12 weeks
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.
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