Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Orthopedics, Changshu Hospital Affiliated to Soochow University, First People's Hospital of Changshu City, Changshu, China.
Front Endocrinol (Lausanne). 2022 Aug 25;13:980867. doi: 10.3389/fendo.2022.980867. eCollection 2022.
Primary osteoporosis has long been underdiagnosed and undertreated. Currently, ferroptosis may be a promising research direction in the prevention and treatment of primary osteoporosis. However, the specific mechanism of ferroptosis in primary osteoporosis remains a mystery. Differentially expressed genes (DEGs) were identified in bone mesenchymal stromal cells (BMSCs) of primary osteoporosis and heathy patients from the GEO databases with the help of bioinformatics analysis. Then, we intersected these DEGs with the ferroptosis dataset and obtained 80 Ferr-DEGs. Several bioinformatics algorithms (PCA, RLE, Limma, BC, MCC, etc.) were adopted to integrate the results. Additionally, we explored the potential functional roles of the Ferr-DEGs GO and KEGG. Protein-protein interactions (PPI) were used to predict potential interactive networks. Finally, 80 Ferr-DEGs and 5 key Ferr-DEGs were calculated. The 5 key Ferr-DEGs were further verified in the OVX mouse model. In conclusion, through a variety of bioinformatics methods, our research successfully identified 5 key Ferr-DEGs associated with primary osteoporosis and ferroptosis, namely, sirtuin 1(), heat shock protein family A () member 5 (), mechanistic target of rapamycin kinase (), hypoxia inducible factor 1 subunit alpha () and beclin 1 (), which were verified in an animal model.
原发性骨质疏松症长期以来一直被漏诊和治疗不足。目前,铁死亡可能是原发性骨质疏松症防治的一个有前途的研究方向。然而,原发性骨质疏松症中铁死亡的确切机制仍是一个谜。本研究借助生物信息学分析,从 GEO 数据库中鉴定出原发性骨质疏松症和健康患者的骨髓间充质基质细胞(BMSCs)中的差异表达基因(DEGs)。然后,我们将这些 DEGs 与铁死亡数据集相交,获得了 80 个 Ferr-DEGs。采用了几种生物信息学算法(PCA、RLE、Limma、BC、MCC 等)对结果进行整合。此外,我们还探讨了 Ferr-DEGs 的潜在功能作用,进行了 GO 和 KEGG 分析。使用蛋白质-蛋白质相互作用(PPI)来预测潜在的相互作用网络。最后,计算了 80 个 Ferr-DEGs 和 5 个关键 Ferr-DEGs。进一步在 OVX 小鼠模型中验证了 5 个关键 Ferr-DEGs。总之,通过多种生物信息学方法,我们的研究成功鉴定出与原发性骨质疏松症和铁死亡相关的 5 个关键 Ferr-DEGs,即沉默调节蛋白 1()、热休克蛋白家族 A()成员 5()、雷帕霉素靶蛋白激酶()、缺氧诱导因子 1 亚基α()和自噬相关蛋白 1(),在动物模型中得到了验证。