目的: 探究继发性酒精性骨质疏松症(AOP)发病中组蛋白H3K27me3甲基化修饰的潜在作用。方法: 利用ChIP-Seq技术检测了骨密度正常(1例)、非AOP(1例)和AOP(1例)共3例男性研究对象的股骨头松质骨中H3K27me3的甲基化水平,通过David数据库进行GO和KEGG信号通路分析,利用STRING数据库进行PPI网络分析,通过VEENY数据库进行多组数据交集分析绘制韦恩图。筛选影响AOP和非AOP病程进展的关键基因和信号通路,初步探讨AOP发生的可能机制。结果: 与正常对照组相比,非AOP组和AOP组H3K27me3修饰均减少,但非AOP组降低更加明显。在AOP组和非AOP组中特异性表达的基因可能与其特定的病理表型或机制相关。通过关键基因的蛋白相互作用网络分析和GO富集分析发现AOP的发生可能与叶酸运输与小G蛋白运输功能障碍密切相关;而非AOP发病则与糖胺聚糖和氨基糖的形成异常相关。结论: 在AOP发生过程中H3K27me3由于维持转录沉默状态程度降低,部分基因转变为激活状态,这可能与酒精造成的骨质损伤有关。通过生物信息学,初步筛选出叶酸可能在酒精性骨质疏松症的发生过程中发挥关键调节作用,有望成为AOP的诊断标志物和治疗靶点。
Objective: To explore the potential role of histone H3K27me3 methylation modification in the pathogenesis of secondary alcoholic-induced osteoporosis (AOP). Methods: ChIP-Seq technology was used to measure H3K27me3 methylation levels in the femoral head cancellous bone of three male subjects, including one with normal bone density, one with non-AOP and one with AOP. GO and KEGG signaling pathway analysis was performed through the David database, PPI network analysis was performed using the STRING database, and multi-group data intersection analysis was performed through the VEENY database to draw the Wayne diagram. In addition, the key genes and signaling pathways affecting the progression of AOP and non-AOP were screened to explore the possible mechanism of AOP. Results: Compared with the normal control group, the H3K27me3 modification was decreased in the non-AOP group and the AOP group, but the decrease was more obvious in the non-AOP group. Differential gene expression analysis revealed that genes specifically expressed in the AOP and non-AOP groups may be associated with their distinct pathological phenotypes or mechanisms. Through protein-protein interaction network analysis and GO enrichment analysis, we fo we found that the occurrence of AOP may be closely related to the dysfunction of folic acid transport and small G protein transport, whereas non-AOP pathogenesis was associated with abnormalities in glycosaminoglycan and amino sugar metabolism. Conclusion: During the development of AOP, H3K27me3, due to a reduced level of transcriptional silencing, leads to the activation of some genes, which may be related to alcohol-induced bone damage. Bioinformatics analysis preliminarily suggests that folic acid may play a key regulatory role in the pathogenesis of AOP, and could potentially serve as a diagnostic biomarker and therapeutic target for AOP.
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