Ma Min, Luo Shulin, Zhou Wei, Lu Liangyu, Cai Junfeng, Yuan Feng, Yin Feng
Tongji University, Department of Orthopaedic Surgery, Shanghai East Hospital, Shanghai, China.
Tongji University, Department of Orthopaedic Surgery, Shanghai East Hospital, Shanghai, China.
Taiwan J Obstet Gynecol. 2017 Apr;56(2):165-170. doi: 10.1016/j.tjog.2016.04.038.
The aim of this study was to gain a better understanding of the molecular mechanisms and identify more critical genes associated with the pathogenesis of postmenopausal osteoporosis (PMOP).
Microarray data of GSE13850 were download from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified either in B cells from postmenopausal female nonsmokers with high bone mineral density (BMD) compared with those with low BMD (defined as DEG1 group) or in B cells from postmenopausal female smokers with high BMD compared with postmenopausal female nonsmokers with high BMD (defined as DEG2 group). Gene ontology and immune-related functional enrichment analysis of DEGs were performed. Additionally, the protein-protein interaction network of all DEGs was constructed and subnetworks of the hub genes were extracted.
A total of 51 DEGs were identified in the DEG1 group, including 30 up- and 21 downregulated genes. Besides, 86 DEGs were identified in the DEG2 group, of which 46 were upregulated and 40 were downregulated. Immune enrichment analysis showed DEGs were mainly enriched in functions of CD molecules and chemokines and receptor, and the upregulated gene interleukin 4 receptor (IL-4R) was significantly enriched. Moreover, guanine nucleotide-binding protein G (GNAI2), filamin A alpha (FLNA), and transforming growth factor-β1 (TGFB1) were hub proteins in the protein-protein interaction network.
IL-4R, GNAI2, FLNA, and TGFB1 may be potential target genes associated with the pathogenesis of PMOP. In particular, FLNA, and TGFB1 may be affected by smoking, a risk factor of PMOP.
本研究旨在更好地理解分子机制，并鉴定出更多与绝经后骨质疏松症（PMOP）发病机制相关的关键基因。
从基因表达综合数据库下载GSE13850的微阵列数据。在骨密度高的绝经后非吸烟女性的B细胞与骨密度低的绝经后非吸烟女性的B细胞（定义为DEG1组）之间，或者在骨密度高的绝经后吸烟女性的B细胞与骨密度高的绝经后非吸烟女性的B细胞之间（定义为DEG2组）鉴定差异表达基因（DEG）。对DEG进行基因本体和免疫相关功能富集分析。此外，构建所有DEG的蛋白质-蛋白质相互作用网络，并提取枢纽基因的子网络。
在DEG1组中总共鉴定出51个DEG，包括30个上调基因和21个下调基因。此外，在DEG2组中鉴定出86个DEG，其中46个上调，40个下调。免疫富集分析显示DEG主要富集于CD分子、趋化因子及其受体的功能，上调基因白细胞介素4受体（IL-4R）显著富集。此外，鸟嘌呤核苷酸结合蛋白G（GNAI2）、细丝蛋白Aα（FLNA）和转化生长因子-β1（TGFB1）是蛋白质-蛋白质相互作用网络中的枢纽蛋白。
IL-4R、GNAI2、FLNA和TGFB1可能是与PMOP发病机制相关的潜在靶基因。特别是，FLNA和TGFB1可能受吸烟影响，吸烟是PMOP的一个风险因素。
