Abstract

Osteoporosis is a major public health problem that is associated with high morbidity and mortality, and its prevalence is increasing as the world’s population ages. Therefore, understanding the molecular basis of the disease is becoming a high priority. In this regard, studies have shown that an imbalance in adipogenic and osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs) is associated with osteoporosis. In this study, we conducted a Weighted Gene Co-Expression Network Analysis to identify gene modules associated with the differentiation of bone marrow MSCs. Gene Ontology and Kyoto Encyclopedia of Genes and Genome enrichment analysis showed that the most significant module, the brown module, was enriched with genes involved in cell cycle regulation, which is in line with the initial results published using these data. In addition, the Cytoscape platform was used to identify important hub genes and lncRNAs correlated with the gene modules. Furthermore, differential gene expression analysis identified 157 and 40 genes that were upregulated and downregulated, respectively, after 3 h of MSCs differentiation. Interestingly, regulatory network analysis, and comparison of the differentially expressed genes with those in the brown module identified potential novel biomarker genes, including two transcription factors (ZNF740, FOS) and two hub genes (FOXQ1, SGK1), which were further validated for differential expression in another data set of differentiation of MSCs. Finally, Gene Set Enrichment Analysis suggested that the two most important candidate hub genes are involved in regulatory pathways, such as the JAK-STAT and RAS signaling pathways. In summary, we have revealed new molecular mechanisms of MSCs differentiation and identified novel genes that could be used as potential therapeutic targets for the treatment of osteoporosis.

Highlights

  • Osteoporosis is a systemic metabolic bone disease characterized by reduction in bone mass and degeneration of bone microstructure, which makes the bone brittle and prone to fracture

  • While osteoclasts are derived from hematopoietic stem cell precursors, osteoblasts and adipocytes are derived from bone marrow mesenchymal stem cells (MSCs) (Chen et al, 2016b)

  • The results showed that many pathways and biological processes are related to mesenchymal cell differentiation, stem cell differentiation, and bone development

Read more

Summary

INTRODUCTION

Osteoporosis is a systemic metabolic bone disease characterized by reduction in bone mass and degeneration of bone microstructure, which makes the bone brittle and prone to fracture. The Gene Expression Omnibus (GEO) database is considered the most comprehensive public repository of large-scale genomics data These databases allow for mining meaningful genomic changes and for discovering biological mechanisms that are involved in disease development and progression (Gruebner et al, 2017). Weighted Gene Co-Expression Network Analysis (WGCNA) is a widely used technique for transcriptomic data analysis (Langfelder & Horvath, 2008) It is a new systems biology approach that is frequently used to study the time course of cell differentiation and biological development (Li et al, 2017; Liu et al, 2017; Tao et al, 2018). Biological enrichment analysis on modules of interest and their corresponding hub genes identified potential key driver genes that could be used as biomarkers and therapeutic targets of osteoporosis

MATERIALS AND METHODS
RESULTS
DISCUSSION
CONCLUSION
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call