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长链非编码 RNA LINC-PINT 在延迟骨折愈合中的功能机制及临床意义

Functional Mechanism and Clinical Implications of lncRNA LINC-PINT in Delayed Fracture Healing.

机构信息

Guizhou University Medical College, Guizhou, China.

Department of Tuina, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.

出版信息

J Invest Surg. 2024 Dec;37(1):2421826. doi: 10.1080/08941939.2024.2421826. Epub 2024 Oct 28.

Abstract

BACKGROUND

Fracture healing can be impeded or even compromised by various factors, resulting in a growing number of patients suffering. The lncRNA LINC-PINT has garnered attention for its latent role in enhancing fracture healing, but its specific functions in this process remain unclear.

OBJECTIVES

The primary objective of this study is to investigate the clinical relevance and underlying molecular mechanisms of LINC-PINT in delayed fracture healing (DFH), while also assessing its potential as an early diagnostic biomarker.

MATERIALS AND METHODS

The expression levels of LINC-PINT were measured in the serum of DFH patients and those with normal fracture healing using RT-qPCR. In MC3T3-E1 cells, the study investigated the influence on the expression of differentiation-related protein, cell viability, and apoptosis through the modulation of LINC-PINT and miR-324-3p. To elucidate the targeting relationship between LINC-PINT, miR-324-3p, and BMP2, a dual-luciferase reporter assay was employed.

RESULTS

The findings revealed a significant downregulation of LINC-PINT expression in DFH patients. LINC-PINT showed high sensitivity and specificity as a diagnostic marker for DFH. In MC3T3-E1 cells, LINC-PINT overexpression markedly enhanced the expression levels of ALP, OCN, Runx2, and OPN, improved cell viability, and inhibited apoptosis. LINC-PINT negatively regulated miR-324-3p, and the effects of LINC-PINT were counteracted by miR-324-3p. LINC-PINT was found to regulate BMP2 by targeting miR-324-3p.

CONCLUSION

LINC-PINT could serve as an early diagnostic biomarker for DFH and slow the progression of DFH by modulating BMP2 through the targeted regulation of miR-324-3p. This research presents new molecular targets for the diagnosis and treatment of DFH.

摘要

背景

骨折愈合过程可能会受到多种因素的阻碍甚至损害,导致越来越多的患者受到影响。LINC-PINT 在促进骨折愈合方面的潜在作用引起了关注,但它在这一过程中的具体功能仍不清楚。

目的

本研究旨在探讨 LINC-PINT 在延迟性骨折愈合(DFH)中的临床相关性和潜在分子机制,并评估其作为早期诊断生物标志物的潜力。

材料和方法

采用 RT-qPCR 检测 DFH 患者和骨折愈合正常患者血清中 LINC-PINT 的表达水平。在 MC3T3-E1 细胞中,通过调节 LINC-PINT 和 miR-324-3p 来研究其对分化相关蛋白表达、细胞活力和细胞凋亡的影响。采用双荧光素酶报告基因实验阐明 LINC-PINT、miR-324-3p 和 BMP2 之间的靶向关系。

结果

研究发现 DFH 患者 LINC-PINT 表达明显下调。LINC-PINT 作为 DFH 的诊断标志物具有较高的灵敏度和特异性。在 MC3T3-E1 细胞中,过表达 LINC-PINT 可显著上调 ALP、OCN、Runx2 和 OPN 的表达水平,提高细胞活力,抑制细胞凋亡。LINC-PINT 负调控 miR-324-3p,miR-324-3p 可拮抗 LINC-PINT 的作用。LINC-PINT 通过靶向 miR-324-3p 调节 BMP2。

结论

LINC-PINT 可作为 DFH 的早期诊断生物标志物,通过靶向调节 miR-324-3p 调控 BMP2 来减缓 DFH 的进展。本研究为 DFH 的诊断和治疗提供了新的分子靶点。

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