Identification of candidate genes in osteoporosis by integrated microarray analysis

Abstract

ObjectivesIn order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis.MethodsWe searched the Gene Expression Omnibus (GEO) database for microarray studies of peripheral blood mononuclear cells in patients with osteoporosis. Subsequently, we integrated gene expression data sets from multiple microarray studies to obtain differentially expressed genes (DEGs) between patients with osteoporosis and normal controls. Gene function analysis was performed to uncover the functions of identified DEGs.ResultsA total of three microarray studies were selected for integrated analysis. In all, 1125 genes were found to be significantly differentially expressed between osteoporosis patients and normal controls, with 373 upregulated and 752 downregulated genes. Positive regulation of the cellular amino metabolic process (gene ontology (GO): 0033240, false discovery rate (FDR) = 1.00E + 00) was significantly enriched under the GO category for biological processes, while for molecular functions, flavin adenine dinucleotide binding (GO: 0050660, FDR = 3.66E-01) and androgen receptor binding (GO: 0050681, FDR = 6.35E-01) were significantly enriched. DEGs were enriched in many osteoporosis-related signalling pathways, including those of mitogen-activated protein kinase (MAPK) and calcium. Protein-protein interaction (PPI) network analysis showed that the significant hub proteins contained ubiquitin specific peptidase 9, X-linked (Degree = 99), ubiquitin specific peptidase 19 (Degree = 57) and ubiquitin conjugating enzyme E2 B (Degree = 57).ConclusionAnalysis of gene function of identified differentially expressed genes may expand our understanding of fundamental mechanisms leading to osteoporosis. Moreover, significantly enriched pathways, such as MAPK and calcium, may involve in osteoporosis through osteoblastic differentiation and bone formation.Cite this article: J. J. Li, B. Q. Wang, Q. Fei, Y. Yang, D. Li. Identification of candidate genes in osteoporosis by integrated microarray analysis. Bone Joint Res 2016;5:594–601. DOI: 10.1302/2046-3758.512.BJR-2016-0073.R1.

The influence of age and osteoporosis on bone marrow stem cells from rats

“…There is contradictory data on the differentiation potential of MSCs from young and aged rats. With identifiable differences in gene expression, 22 , 23 we had hypothesized that MSCs from OVX rats would have lower osteogenic potential and would more likely differentiate to adipocytes compared with MSCs from young rats; however, this was not the case. MSCs from OVX rats had lower osteogenic differentiation potential, but they also had a lower adipogenic differentiation ability compared with MSCs from young rats.…”

The role of CKIP-1 in osteoporosis development and treatment

“…These factors include numerous cytokines and signalling pathways, such as nuclear receptor-interacting protein 1 (NRIP1), interleukin-1 receptor-associated kinase 3 (IRAK3), bone morphogenetic protein 7 (BMP7), SMAD family member 1 (SMAD1), MAPK3,C-X-C chemokine receptor type 4 (CXCR4), OPG/RANKL/RANKL pathway, Wnt/β-catenin pathway, cathepsin K pathway, and BMP pathway. 27 , 28 The BMP pathway is the most important signalling during these processes, as it can induce osteogenic differentiation, enhance bone formation without activating resorption and can promote bone repair without affecting non-skeletal tissues. 29 …”

Investigation of long non‑coding RNA expression profiles in patients with post‑menopausal osteoporosis by RNA sequencing

“…The results suggested that the differentially expressed lncRNAs were accumulated in PMOP-associated signaling pathways, including osteoclast differentiation, as well as TNF and MAPK signaling pathways. Aberrant gene expression profiles have been observed in various diseases, suggesting their potential as diagnostic biomarkers and therapeutic targets (15)(16)(17). The gene expression profiles in osteoporosis remain poorly investigated.…”