Devision of Orthopeadic Surgery, the University of Alberta, Edmonton, Alberta, T6G 2R3, Canada.
The National Key Discipline and the Orthopedic Laboratory, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, P.R. China.
Sci Rep. 2019 Dec 12;9(1):18926. doi: 10.1038/s41598-019-55188-6.
Serum miRNAs are potential biomarkers for predicting the progress of bone diseases, but little is known about miRNAs in alcohol-induced osteonecrosis of femoral head (AIONFH). This study evaluated disease-prevention value of specific serum miRNA expression profiles in AIONFH. MiRNA PCR Panel was taken to explore specific miRNAs in serum of AIONFH cases. The top differentially miRNAs were further validated by RT-qPCR assay in serum and bone tissues of two independent cohorts. Their biofunction and target genes were predicted by bioinformatics databases. Target genes related with angiogenesis and osteogenesis were quantified by RT-qPCR in necrotic bone tissue. Our findings demonstrated that multiple miRNAs were evaluated to be differentially expressed with high dignostic values. MiR-127-3p, miR-628-3p, and miR-1 were downregulated, whereas miR-885-5p, miR-483-3p, and miR-483-5p were upregulated in serum and bone samples from the AIONFH patients compared to those from the normal control individuals (p < 0.01). The predicted target genes of the indicated miRNAs quantified by qRT-PCR, including IGF2, PDGFA, RUNX2, PTEN, and VEGF, were presumed to be altered in necrotic bone tissue of AIONFH patients. The presence of five altered miRNAs in AIONFH patients may serve as non-invasive biomarkers and potential therapeutic targets for the early diagnosis of AIONFH.
血清 miRNAs 是预测骨疾病进展的潜在生物标志物，但关于酒精性股骨头坏死 (AIONFH) 中的 miRNAs 知之甚少。本研究评估了特定血清 miRNA 表达谱在 AIONFH 中的疾病预防价值。采用 miRNA PCR 面板探讨 AIONFH 患者血清中的特定 miRNA。通过 RT-qPCR 检测在两个独立队列的血清和骨组织中进一步验证 top 差异表达 miRNA。通过生物信息学数据库预测其生物功能和靶基因。通过 RT-qPCR 定量检测坏死骨组织中与血管生成和成骨相关的靶基因。研究结果表明，多种 miRNA 被评估为具有高诊断价值的差异表达。与正常对照组相比，AIONFH 患者的血清和骨样本中 miR-127-3p、miR-628-3p 和 miR-1 下调，而 miR-885-5p、miR-483-3p 和 miR-483-5p 上调 (p<0.01)。通过 qRT-PCR 定量的指示 miRNA 的预测靶基因，包括 IGF2、PDGFA、RUNX2、PTEN 和 VEGF，被认为在 AIONFH 患者的坏死骨组织中发生改变。五种改变的 miRNA 在 AIONFH 患者中的存在可能作为 AIONFH 的早期诊断的非侵入性生物标志物和潜在治疗靶点。
