Identification of crucial genes related to postmenopausal osteoporosis using gene expression profiling

Aging Clin Exp Res. 2016 Dec;28(6):1067-1074. doi: 10.1007/s40520-015-0509-y. Epub 2015 Dec 16.


Background: Postmenopausal osteoporosis is a common bone disease and characterized by low bone mineral density.

Aim: This study aimed to reveal key genes associated with postmenopausal osteoporosis (PMO), and provide a theoretical basis for subsequent experiments.

Methods: The dataset GSE7429 was obtained from Gene Expression Omnibus. A total of 20 B cell samples (ten ones, respectively from postmenopausal women with low or high bone mineral density (BMD) were included in this dataset. Following screening of differentially expressed genes (DEGs), coexpression analysis of all genes was performed, and key genes in the coexpression network were screened using the random walk algorithm. Afterwards, functional and pathway analyses were conducted. Additionally, protein-protein interactions (PPIs) between DEGs and key genes were analyzed.

Results: A set of 308 DEGs (170 up-regulated ones and 138 down-regulated ones) between low BMD and high BMD samples were identified, and 101 key genes in the coexpression network were screened out. In the coexpression network, some genes had a higher score and degree, such as CSTA. The key genes in the coexpression network were mainly enriched in GO terms of the defense response (e.g., SERPINA1 and CST3), immune response (e.g., IL32 and CLEC7A); while, the DEGs were mainly enriched in structural constituent of cytoskeleton (e.g., CYLC2 and TUBA1B) and membrane-enclosed lumen (e.g., CCNE1 and INTS5). In the PPI network, CCNE1 interacted with REL; and TUBA1B interacted with ESR1.

Conclusions: A series of interactions, such as CSTA/TYROBP, CCNE1/REL and TUBA1B/ESR1 might play pivotal roles in the occurrence and development of PMO.

Keywords: Coexpression; Differentially expressed gene; Network; Postmenopausal osteoporosis; Protein–protein interaction.

MeSH terms

  • Aged
  • Bone Density*
  • Down-Regulation
  • Female
  • Gene Expression
  • Gene Expression Profiling / methods
  • Genetic Predisposition to Disease
  • Humans
  • Middle Aged
  • Osteoporosis, Postmenopausal* / diagnosis
  • Osteoporosis, Postmenopausal* / genetics
  • Osteoporosis, Postmenopausal* / physiopathology
  • Protein Interaction Maps
  • Up-Regulation