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09 May 2015 : Laboratory Research

Identification of Transcriptional Factors and Key Genes in Primary Osteoporosis by DNA Microarray

Wengui XieABCDEFG, Lixin JiABCDE, Teng ZhaoABCDEFG, Pengfei GaoABCDEFG

DOI: 10.12659/MSM.894111

Med Sci Monit 2015; 21:1333-1344

Abstract

BACKGROUND: A number of genes have been identified to be related with primary osteoporosis while less is known about the comprehensive interactions between regulating genes and proteins. We aimed to identify the differentially expressed genes (DEGs) and regulatory effects of transcription factors (TFs) involved in primary osteoporosis.

MATERIAL AND METHODS: The gene expression profile GSE35958 was obtained from Gene Expression Omnibus database, including 5 primary osteoporosis and 4 normal bone tissues. The differentially expressed genes between primary osteoporosis and normal bone tissues were identified by the same package in R language. The TFs of these DEGs were predicted with the Essaghir A method. DAVID (The Database for Annotation, Visualization and Integrated Discovery) was applied to perform the GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis of DEGs. After analyzing regulatory effects, a regulatory network was built between TFs and the related DEGs.

RESULTS: A total of 579 DEGs was screened, including 310 up-regulated genes and 269 down-regulated genes in primary osteoporosis samples. In GO terms, more up-regulated genes were enriched in transcription regulator activity, and secondly in transcription factor activity. A total 10 significant pathways were enriched in KEGG analysis, including colorectal cancer, Wnt signaling pathway, Focal adhesion, and MAPK signaling pathway. Moreover, total 7 TFs were enriched, of which CTNNB1, SP1, and TP53 regulated most up-regulated DEGs.

CONCLUSIONS: The discovery of the enriched TFs might contribute to the understanding of the mechanism of primary osteoporosis. Further research on genes and TFs related to the WNT signaling pathway and MAPK pathway is urgent for clinical diagnosis and directing treatment of primary osteoporosis.

Keywords: Aged, 80 and over, Cells, Cultured, Databases, Genetic, Femur Head - pathology, Gene Expression Profiling, gene ontology, Gene Regulatory Networks, Genes, Mesenchymal Stromal Cells - metabolism, Oligonucleotide Array Sequence Analysis, Osteoporosis - genetics, Osteoporosis, Postmenopausal - genetics, Signal Transduction - genetics, Transcription Factors - genetics

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750