Abstract
BackgroundPrimary osteoporosis is an age-related disease, and the main cause of this disease is the failure of bone homeostasis. Previous studies have shown that primary osteoporosis is associated with gene mutations.To explore the functional modules of the PPI (protein-protein interaction) network of differentially expressed genes (DEGs), and the related pathways participating in primary osteoporosis.MethodsThe gene expression profile of primary osteoporosis GSE35956 was downloaded from the GEO (Gene Expression Omnibus) database and included five MSC (mesenchymal stem cell) specimens of normal osseous tissue and five MSC specimens of osteoporosis. The DEGs between the two types of MSC specimens were identified by the samr package in R language. In addition, the functions and pathways of DEGs were enriched. Then the DEGs were mapped to String to acquire PPI pairs and the PPI network was constructed with by these PPI pairs. Topological properties of the network were calculated by Network Analyzer, and modules in the network were screened by Cluster ONE software. Subsequently, the fronting five modules whose P-value was less than 1.0e-05 were identified and function analysis was conducted.ResultsA total of 797 genes were filtered as DEGs from these ten specimens of GSE35956 with 660 up-regulated genes and 137 down-regulated genes. Meanwhile, up-regulated DEGs were mainly enriched in functions and pathways related to cell cycle and DNA replication. Furthermore, there were 4,135 PPI pairs and 377 nodes in the PPI network. Four modules were enriched in different pathways, including cell cycle and DNA replication pathway in module 2.ConclusionsIn this paper, we explored the genes and pathways involved in primary osteoporosis based on gene expression profiles, and the present findings have the potential to be used clinically for the future treatment of primary osteoporosis.
Highlights
Primary osteoporosis is an age-related disease, and the main cause of this disease is the failure of bone homeostasis
Previous studies have found that the mutations of genes such as those for macrophage colony stimulating factor 1 (CSF1) [2] and FTH1 [3], and osteoporosis-related genes such as COL1A1 [4], lipoprotein receptor-related protein 5 (LRP5) [4], runt related transcription factor 2 (RUNX2) [5], winglessrelated MMTV integration site 3A (WNT3A) [6], abstract dickkopf-1 (DKK1) [6], and receptor activator of nuclear factor-kB ligand (RANKL) [7] are related to primary osteoporosis
Function and pathway annotation of differentially expressed genes (DEGs) By the analysis of Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs, we found that up-regulated genes and downregulated genes were significantly enriched in different GO terms and KEGG pathways
Summary
Primary osteoporosis is an age-related disease, and the main cause of this disease is the failure of bone homeostasis. Previous studies have shown that primary osteoporosis is associated with gene mutations. Previous studies have found that the mutations of genes such as those for CSF1 (macrophage colony stimulating factor 1) [2] and FTH1 (ferritin, heavy polypeptide 1) [3], and osteoporosis-related genes such as COL1A1 (collagen, type, alpha 1) [4], LRP5 (low-density lipoprotein receptor-related protein 5) [4], RUNX2 (runt related transcription factor 2) [5], WNT3A (wingless-related MMTV integration site 3A) [6], DKK1 (abstract dickkopf-1) [6], and RANKL (receptor activator of NF-kB ligand) [7] are related to primary osteoporosis. Low-density lipoprotein receptor-related protein 5 (LRP5) effects the development of primary osteoporosis by altering bone mineral density [8]. Previous studies have identified several potential genes and proteins as determinants of peak bone mass and susceptibility for osteoporosis, the studies on primary osteoporosis are still in their early stages
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