Department of Orthopedic Surgery, Tongji Hospital, Tongji University, Shanghai 200065, P.R. China.
Mol Med Rep. 2018 Jan;17(1):1561-1572. doi: 10.3892/mmr.2017.8045. Epub 2017 Nov 14.
The present study aimed to determine candidate genes, chemicals and mechanisms underlying postmenopausal osteoporosis (PMOP). A gene expression profile (accession no. GSE68303), which included 12 tissue samples from ovariectomized mice (OVX group) and 11 normal tissue samples from sham surgery mice (control group), was downloaded from the Gene Expression Omnibus database. The identification of differentially expressed genes (DEGs), and Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses, was performed, followed by an investigation of protein‑protein interactions (PPI), PPI modules, transcription factors (TFs) and chemicals. A total of 784 upregulated and 729 downregulated DEGs between the two groups were identified. Furthermore, 2 upregulated modules and 6 downregulated modules were determined. The upregulated DEGs in modules were enriched in 'sensory perception of smell' function and 'olfactory transduction' pathway, and a number of genes belonging to the olfactory receptor (OLFR) family were identified in upregulated modules. The downregulated DEGs in modules were enriched in 'DNA replication initiation' function and 'cell cycle' pathway. A total of 8 TFs, including SP1 TF (SP1) and protein C‑ets‑1 (ETS1), were associated with PMOP. Furthermore, estradiol and resveratrol were identified as key chemicals in the chemical‑gene interaction network. Therefore, TFs, including SP1 and ETS1, in addition to members of the OLFR gene family, may be employed as novel targets for treatment of PMOP. Furthermore, functions including 'sensory perception of smell' and 'replication initiation', and 'olfactory transduction' and 'cell cycle' pathways, may serve roles in PMOP. In addition, based on the chemical‑gene interaction network, estradiol and resveratrol may also be considered for the treatment PMOP.
本研究旨在确定绝经后骨质疏松症(PMOP)的候选基因、化学物质和机制。从基因表达综合数据库(GEO)下载了一个基因表达谱(注册号 GSE68303),其中包括 12 个去势小鼠(OVX 组)组织样本和 11 个假手术小鼠(对照组)的正常组织样本。进行了差异表达基因(DEG)的鉴定、基因本体论(GO)功能富集和京都基因与基因组百科全书(KEGG)通路分析,随后研究了蛋白质-蛋白质相互作用(PPI)、PPI 模块、转录因子(TF)和化学物质。两组间共鉴定出 784 个上调 DEG 和 729 个下调 DEG。此外,还确定了 2 个上调模块和 6 个下调模块。模块中的上调 DEG 富集于“嗅觉感觉”功能和“嗅觉转导”通路,并且鉴定出一些属于嗅觉受体(OLFR)家族的基因存在于上调模块中。模块中的下调 DEG 富集于“DNA 复制起始”功能和“细胞周期”通路。共有 8 个 TF,包括 SP1 转录因子(SP1)和蛋白 C-ets-1(ETS1),与 PMOP 相关。此外,鉴定出雌二醇和白藜芦醇为化学-基因相互作用网络中的关键化学物质。因此,包括 SP1 和 ETS1 在内的 TF 以及 OLFR 基因家族的成员,可能被用作治疗 PMOP 的新靶点。此外,“嗅觉感觉”和“复制起始”等功能以及“嗅觉转导”和“细胞周期”通路可能在 PMOP 中发挥作用。此外,基于化学-基因相互作用网络,雌二醇和白藜芦醇也可考虑用于治疗 PMOP。