Department of Spine Surgery, General Hospital of Ningxia Medical University, Ningxia, China.
Clinical College of Ningxia Medical University, Ningxia, China.
Spine (Phila Pa 1976). 2023 Sep 15;48(18):E317-E328. doi: 10.1097/BRS.0000000000004763. Epub 2023 Jun 27.
Basic science laboratory study.
To identify hub genes related to bone morphogenetic proteins (BMPs) in the ossification of the ligamentum flavum (OLF) and analyze their functional characteristics.
The exact etiology and pathologic mechanism of OLF remain unclear. BMPs are pleiotropic osteoinductive proteins that may play a critical role in this condition.
The GSE106253 and GSE106256 data sets were downloaded from the Gene Expression Omnibus database. The messenger RNA (mRNA) and long noncoding RNA expression profiles were obtained from GSE106253. The microRNA expression profiles were obtained from GSE106256. Differentially expressed genes were identified between OLF and non-OLF groups and then intersected with BMP-related genes to obtain differentially expressed BMP-related genes. The least absolute shrinkage selection operator and support vector machine recursive feature elimination were used to screen hub genes. Furthermore, a competing endogenous RNA network was constructed to explain the expression regulation of the hub genes in OLF. Finally, the protein and mRNA expression levels of the hub genes were verified using Western blot and real-time polymerase chain reaction, respectively.
We identified 671 Differentially expressed genes and 32 differentially expressed BMP-related genes. Hub genes ADIPOQ , SCD , SCX , RPS18 , WDR82 , and SPON1 , identified through the least absolute shrinkage selection operator and support vector machine recursive feature elimination analyses, showed high diagnostic values for OLF. Furthermore, the competing endogenous RNA network revealed the regulatory mechanisms of the hub genes. Real-time polymerase chain reaction showed that the mRNA expression of the hub genes was significantly downregulated in the OLF group compared with the non-OLF group. Western blot showed that the protein levels of ADIPOQ, SCD, WDR82 , and SPON1 were significantly downregulated, whereas those of SCX and RPS18 were significantly upregulated in the OLF group compared with the non-OLF group.
This study is the first to identify BMP-related genes in OLF pathogenesis through bioinformatics analysis. ADIPOQ , SCD , SCX , RPS18 , WDR82 , and SPON1 were identified as hub genes for OLF. The identified genes may serve as potential therapeutic targets for treating patients with OLF.
基础科学实验室研究。
鉴定与骨形态发生蛋白（BMPs）相关的韧带骨化（OLF）中的枢纽基因，并分析其功能特征。
OLF 的确切病因和病理机制尚不清楚。BMP 是多效性的成骨诱导蛋白，在这种情况下可能发挥关键作用。
从基因表达综合数据库中下载 GSE106253 和 GSE106256 数据集。从 GSE106253 中获得信使 RNA（mRNA）和长非编码 RNA 表达谱。从 GSE106256 中获得 microRNA 表达谱。在 OLF 和非 OLF 组之间鉴定差异表达基因，然后与 BMP 相关基因相交，获得差异表达的 BMP 相关基因。使用最小绝对收缩选择算子和支持向量机递归特征消除来筛选枢纽基因。此外，构建竞争性内源性 RNA 网络以解释 OLF 中枢纽基因的表达调控。最后，分别通过 Western blot 和实时聚合酶链反应验证枢纽基因的蛋白和 mRNA 表达水平。
我们鉴定了 671 个差异表达基因和 32 个差异表达的 BMP 相关基因。通过最小绝对收缩选择算子和支持向量机递归特征消除分析鉴定的枢纽基因 ADIPOQ、SCD、SCX、RPS18、WDR82 和 SPON1 对 OLF 具有较高的诊断价值。此外，竞争性内源性 RNA 网络揭示了枢纽基因的调控机制。实时聚合酶链反应显示，与非 OLF 组相比，OLF 组中枢纽基因的 mRNA 表达显著下调。Western blot 显示，与非 OLF 组相比，OLF 组中 ADIPOQ、SCD、WDR82 和 SPON1 的蛋白水平显著下调，而 SCX 和 RPS18 的蛋白水平显著上调。
本研究首次通过生物信息学分析鉴定了 OLF 发病机制中的 BMP 相关基因。ADIPOQ、SCD、SCX、RPS18、WDR82 和 SPON1 被鉴定为 OLF 的枢纽基因。鉴定出的基因可能成为治疗 OLF 患者的潜在治疗靶点。
