Qi Jing, Liu E, Pang Yunqing, Wang Yu, Wang Jing
The First School of Clinical Medicine, Lanzhou University, 1 Donggang West Road, Chengguan District, Lanzhou, Gansu, China.
Stomatology Center of Gansu Provincial Hospital, 204 Donggang West Road, Chengguan District, Lanzhou, Gansu, China.
Sci Rep. 2025 Aug 5;15(1):28479. doi: 10.1038/s41598-025-13872-w.
Postmenopausal osteoporosis (PMOP) increases the risk of periodontitis (PD), yet the shared mechanisms remain unclear. Rho-signal transduction genes may play a role due to their involvement in bone remodeling. This study aimed to explore Rho-related genes as potential biomarkers linking PMOP and PD. Public transcriptomic datasets of PMOP and PD were analyzed. After PCA-based outlier removal, differentially expressed genes were identified using limma, followed by intersection analysis, KEGG enrichment, PPI network construction, and Rho pathway screening. Machine learning (Lasso, SVM-RFE) and Wilcoxon tests identified CTNNAL1 and MERTK as candidate biomarkers. GSEA, ssGSEA, and immune infiltration analyses were performed, along with construction of lncRNA/circRNA-miRNA-mRNA regulatory networks. Subcellular localization, chromosomal mapping, disease association, and molecular docking analyses were also conducted. An ovariectomy plus periodontitis (OP+PD) mouse model was used for in vivo validation. CTNNAL1 and MERTK were consistently dysregulated in both PMOP and PD datasets. They were enriched in MYC-targets-V1, allograft rejection, heme metabolism, and oxidative phosphorylation. Immune analysis revealed altered levels of CD56^bright NK cells and immature dendritic cells. Regulatory networks implicated lncRNAs such as XIST, GAS5, and NEAT1. Molecular docking indicated interactions with pinosylvin and glycitein. In vivo validation confirmed significant changes in CTNNAL1 and MERTK expression and increased bone loss and inflammation in OP+PD mice. CTNNAL1 and MERTK were identified as potential Rho-associated biomarkers showing consistent dysregulation in both PMOP and PD datasets. These biomarkers may serve as risk indicators or therapeutic candidates, warranting further validation.
绝经后骨质疏松症（PMOP）会增加患牙周炎（PD）的风险，但其共同机制仍不清楚。Rho信号转导基因可能因其参与骨重塑而发挥作用。本研究旨在探索Rho相关基因作为连接PMOP和PD的潜在生物标志物。分析了PMOP和PD的公共转录组数据集。在基于主成分分析（PCA）去除异常值后，使用limma鉴定差异表达基因，随后进行交集分析、KEGG富集、蛋白质-蛋白质相互作用（PPI）网络构建和Rho通路筛选。机器学习（套索回归、支持向量机递归特征消除法）和Wilcoxon检验确定CTNNAL1和MERTK为候选生物标志物。进行了基因集富集分析（GSEA）、单样本基因集富集分析（ssGSEA）和免疫浸润分析，并构建了长链非编码RNA（lncRNA）/环状RNA（circRNA）-微小RNA（miRNA）-信使RNA（mRNA）调控网络。还进行了亚细胞定位、染色体定位、疾病关联和分子对接分析。使用卵巢切除加牙周炎（OP+PD）小鼠模型进行体内验证。CTNNAL1和MERTK在PMOP和PD数据集中均持续失调。它们在MYC靶标-V1、同种异体移植排斥、血红素代谢和氧化磷酸化中富集。免疫分析显示CD56^bright自然杀伤（NK）细胞和未成熟树突状细胞水平发生改变。调控网络涉及XIST、GAS5和NEAT1等lncRNA。分子对接表明与松素和大豆黄素存在相互作用。体内验证证实CTNNAL1和MERTK表达有显著变化，且OP+PD小鼠的骨质流失和炎症增加。CTNNAL1和MERTK被确定为潜在的Rho相关生物标志物，在PMOP和PD数据集中均表现出一致的失调。这些生物标志物可作为风险指标或治疗候选物，值得进一步验证。
