Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon 16499, Korea.
Ajou Institute on Aging, Ajou University Medical Center, Suwon 16499, Korea.
Genes (Basel). 2022 Mar 3;13(3):459. doi: 10.3390/genes13030459.
The systemic gene interactions that occur during osteoporosis and their underlying mechanisms remain to be determined. To this end, mesenchymal stromal cells (MSCs) were analyzed from bone marrow samples collected from healthy individuals ( = 5) and patients with osteoporosis ( = 5). A total of 120 osteoporosis-related genes were identified using RNA-sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) software. In order to analyze these genes, we constructed a heatmap of one-way hierarchical clustering and grouped the gene expression patterns of the samples. The MSCs from one control participant showed a similar expression pattern to that observed in the MSCs of three patients with osteoporosis, suggesting that the differentiating genes might be important genetic determinants of osteoporosis. Then, we selected the top 38 genes based on fold change and expression, excluding osteoporosis-related genes from the control participant. We identified a network among the top 38 genes related to osteoblast and osteoclast differentiation, bone remodeling, osteoporosis, and sarcopenia using the Molecule Activity Predictor program. Among them, 25 genes were essential systemic genes involved in osteoporosis. Furthermore, we identified 24 genes also associated with diabetes and obesity, among which 10 genes were involved in a network related to bone and energy metabolism. The study findings may have implications for the treatment and prevention of osteoporosis.
骨质疏松症发生时的系统基因相互作用及其潜在机制仍有待确定。为此，我们分析了来自健康个体（n=5）和骨质疏松症患者（n=5）骨髓样本中的间充质基质细胞（MSCs）。使用 RNA 测序（RNA-seq）和 IPA 软件鉴定了 120 个与骨质疏松症相关的基因。为了分析这些基因，我们构建了一个单向层次聚类热图，并对样本的基因表达模式进行了分组。一名对照参与者的 MSCs 表现出与三名骨质疏松症患者的 MSCs 相似的表达模式，这表明分化基因可能是骨质疏松症的重要遗传决定因素。然后，我们根据倍数变化和表达选择了前 38 个基因，排除了对照参与者中的骨质疏松症相关基因。我们使用分子活性预测程序鉴定了与成骨细胞和破骨细胞分化、骨重塑、骨质疏松症和肌肉减少症相关的前 38 个基因之间的网络。其中，25 个基因是参与骨质疏松症的重要系统性基因。此外，我们还鉴定了 24 个与糖尿病和肥胖相关的基因，其中 10 个基因参与了与骨和能量代谢相关的网络。该研究结果可能对骨质疏松症的治疗和预防具有重要意义。
