Gu Huijie, Huang Zhongyue, Chen Guangnan, Zhou Kaifeng, Zhang Yiming, Chen Jiong, Xu Jun, Yin Xiaofan
Department of Orthopedics, Minhang Hospital, Fudan University, Shanghai 201199, China.
Medicine (Baltimore). 2020 Feb;99(8):e19120. doi: 10.1097/MD.0000000000019120.
Osteoporosis (OP) is a disease characterized by bone mass loss, bone microstructure damage, increased bone fragility, and easy fracture. The molecular mechanism underlying OP remains unclear.In this study, we identified 217 genes associated with OP, and formed a gene set [OP-related genes gene set (OPgset)].The highly enriched GOs and pathways showed OPgset genes were significantly involved in multiple biological processes (skeletal system development, ossification, and osteoblast differentiation), and several OP-related pathways (Wnt signaling pathway, osteoclast differentiation, steroid hormone biosynthesis, and adipocytokine signaling pathway). Besides, pathway crosstalk analysis indicated three major modules, with first module consisted of pathways mainly involved in bone development-related signaling pathways, second module in Wnt-related signaling pathway and third module in metabolic pathways. Further, we calculated degree centrality of a node and selected ten key genes/proteins, including TGFB1, IL6, WNT3A, TNF, PTH, TP53, WNT1, IGF1, IL10, and SERPINE1. We analyze the K-core and construct three k-core sub-networks of OPgset genes.In summary, we for the first time explored the molecular mechanism underlying OP via network- and pathway-based methods, results from our study will improve our understanding of the pathogenesis of OP. In addition, these methods performed in this study can be used to explore pathogenesis and genes related to a specific disease.
骨质疏松症（OP）是一种以骨量丢失、骨微结构破坏、骨脆性增加和易骨折为特征的疾病。OP的分子机制尚不清楚。在本研究中，我们鉴定了217个与OP相关的基因，并形成了一个基因集[OP相关基因基因集（OPgset）]。高度富集的基因本体（GO）和通路显示OPgset基因显著参与多个生物学过程（骨骼系统发育、骨化和成骨细胞分化）以及几个与OP相关的通路（Wnt信号通路、破骨细胞分化、类固醇激素生物合成和脂肪细胞因子信号通路）。此外，通路串扰分析表明存在三个主要模块，第一个模块由主要参与骨发育相关信号通路的通路组成，第二个模块参与Wnt相关信号通路，第三个模块参与代谢通路。进一步地，我们计算了节点的度中心性并选择了十个关键基因/蛋白质，包括TGFB1、IL6、WNT3A、TNF、PTH、TP53、WNT1、IGF1、IL10和SERPINE1。我们分析了K核并构建了OPgset基因的三个K核子网。总之，我们首次通过基于网络和通路的方法探索了OP的分子机制，我们的研究结果将增进我们对OP发病机制的理解。此外，本研究中使用的这些方法可用于探索与特定疾病相关的发病机制和基因。
