Monocytes affect bone mineral density in pre- and postmenopausal women through ribonucleoprotein complex biogenesis by integrative bioinformatics analysis

Zi-Hang Zeng,Kang-Wen Xiao,Jia-Li Li,Lin Cai,Xin Yan,Zhi-Bo Liu,Zhi-Qiang Hou

doi:10.1038/s41598-019-53843-6

Zi-Hang Zeng, Kang-Wen Xiao + Show 5 more

Open Access

https://doi.org/10.1038/s41598-019-53843-6

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Abstract

Osteoporosis is one of the most common metabolic bone disease among pre- and postmenopausal women. As the precursors of osteoclast cells, circulating monocytes play important role in bone destruction and remodeling. The aim of study is to identify potential key genes and pathways correlated with the pathogenesis of osteoporosis. Then we construct novel estimation model closely linked to the bone mineral density (BMD) with key genes. Weighted gene co-expression network analysis (WGCNA) were conducted by collecting gene data set with 80 samples from gene expression omnibus (GEO) database. Besides, hub genes were identified by series of bioinformatics and machine learning algorithms containing protein-protein interaction (PPI) network, receiver operating characteristic curve and Pearson correlation. The direction of correlation coefficient were performed to screen for gene signatures with high BMD and low BMD. A novel BMD score system was put forward based on gene set variation analysis and logistic regression, which was validated by independent data sets. We identified six modules correlated with BMD. Finally 100 genes were identified as the high bone mineral density signatures while 130 genes were identified as low BMD signatures. Besides, we identified the significant pathway in monocytes: ribonucleoprotein complex biogenesis. What's more, our score validated it successfully.

Highlights

Osteoporosis is one of the most common metabolic bone disease among pre- and postmenopausal women
Raw gene expression data of monocytes in osteoporosis were downloaded from the gene expression omnibus (GEO) database with the accession of GSE56815 and GSE2208, containing 80 and 19 samples, respectively
Ribonucleoprotein complex biogenesis: a significant pathway to bone mineral density (BMD). These 230 genes were used to perform gene set enrichment analysis and the results showed that genes were only significantly enriched in Gene ontology (GO): 0022613 ribonucleoprotein complex biogenesis with the enrichment score (ES) = −0.520 (p = 0.0035, false positive discovery rate (FDR) = 0.040, Fig. 5C)

Summary

Introduction

Osteoporosis is one of the most common metabolic bone disease among pre- and postmenopausal women. The aim of study is to identify potential key genes and pathways correlated with the pathogenesis of osteoporosis. We construct novel estimation model closely linked to the bone mineral density (BMD) with key genes. A novel BMD score system was put forward based on gene set variation analysis and logistic regression, which was validated by independent data sets. Osteoporosis is one of the most common metabolic disease affecting thousands of pre- and postmenopausal women[1]. Circulating monocytes are closely related to pathogenesis of osteoporosis, which have been studied for pathophysiology of bone research in the past several years. Phiel’s study demonstrated that differential estrogen receptor expression was detected in monocytes in pre and postmenopausal women[14]. What’s more, estrogen has been found to inhibit RANKL-stimulated osteoclastic differentiation of monocytes in Perrien’s study[15]

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