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MYLK-AS1 通过靶向 miR-146a-5p 调节成骨细胞的细胞活力和凋亡来改善骨折。

MYLK-AS1 improves fracture by targeting miR-146a-5p to regulate cell viability and apoptosis in osteoblasts.

作者信息

Mahan Wuluhan, Gao Haoze, Liu Ning, Zhao Zhenyu, Huang Yingxuan

机构信息

Department of Orthopedic Trauma, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, China.

The Third Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.

出版信息

J Orthop Surg Res. 2025 Mar 19;20(1):295. doi: 10.1186/s13018-025-05688-1.

Abstract

BACKGROUND

Delayed fracture healing (DFH) is a significant burden for patients. Therefore, early diagnosis and detection are important for the treatment of DFH. The long non-coding RNA (LncRNA) MYLK-AS1 is abnormally expressed in patients with DFH and has the potential to be used as a diagnostic marker.

METHODS

40 patients with DFH and 87 patients with normal fracture healing were included. The levels of MYLK-AS1, miR-146a-5p and several mRNA markers of osteogenic differentiation were assessed by RT-qPCR. The diagnostic value of MYLK-AS1, miR-146a-5p was assessed using ROC curves. Cell proliferation ability was assessed by CCK-8, and apoptosis rate was detected by flow cytometry. DLR, RIP and RNA pull down assays demonstrated the targeting relationship between MYLK-AS1 and miR-146a-5p.

RESULTS

MYLK-AS1 levels were significantly lower and miR-146a-5p levels were significantly up-regulated in DFH compared to normal healing patients. MYLK-AS1 was found to target miR-146a-5p, and the levels were negatively correlated with each other. MYLK-AS1 with miR-146a-5p is of high value for the diagnosis of DFH. High expression of MYLK-AS1 could inhibit miR-146a-5p levels, support cell proliferation, reduce apoptosis, and increase the levels of osteogenesis-specific matrix proteins and osteogenesis-related regulatory factors.

CONCLUSION

MYLK-AS1 has potential as a diagnostic marker for DFH. By increasing the expression level of MYLK-AS1 in cells can reduce the level of miR-146a-5p, increase the activity of osteoblasts and reduce their apoptosis rate, thus affecting the process of fracture healing.

摘要

背景

骨折愈合延迟(DFH)对患者来说是一项重大负担。因此,早期诊断和检测对于DFH的治疗很重要。长链非编码RNA(LncRNA)MYLK-AS1在DFH患者中异常表达,有潜力用作诊断标志物。

方法

纳入40例DFH患者和87例骨折愈合正常的患者。通过RT-qPCR评估MYLK-AS1、miR-146a-5p的水平以及几种成骨分化的mRNA标志物。使用ROC曲线评估MYLK-AS1、miR-146a-5p的诊断价值。通过CCK-8评估细胞增殖能力,通过流式细胞术检测凋亡率。双荧光素酶报告基因(DLR)、RNA免疫沉淀(RIP)和RNA下拉实验证明了MYLK-AS1与miR-146a-5p之间的靶向关系。

结果

与正常愈合患者相比,DFH患者中MYLK-AS1水平显著降低,miR-146a-5p水平显著上调。发现MYLK-AS1靶向miR-146a-5p,且二者水平呈负相关。MYLK-AS1联合miR-146a-5p对DFH诊断具有较高价值。MYLK-AS1的高表达可抑制miR-146a-5p水平,促进细胞增殖,减少凋亡,并增加成骨特异性基质蛋白和成骨相关调节因子的水平。

结论

MYLK-AS1有潜力作为DFH的诊断标志物。通过提高细胞中MYLK-AS1的表达水平可降低miR-146a-5p水平,增加成骨细胞活性并降低其凋亡率,从而影响骨折愈合过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf51/11921714/041a2fd30970/13018_2025_5688_Fig1_HTML.jpg

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