Abstract
Background: Osteoporosis is a highly heritable skeletal muscle disease. However, the genetic mechanisms mediating the pathogenesis of osteoporosis remain unclear. Accordingly, in this study, we aimed to clarify the transcriptional regulation and heritability underlying the onset of osteoporosis.Methods: Transcriptome gene expression data were obtained from the Gene Expression Omnibus database. Microarray data from peripheral blood monocytes of 73 Caucasian women with high and low bone mineral density (BMD) were analyzed. Differentially expressed messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) were identified. Differences in BMD were then attributed to several gene modules using weighted gene co-expression network analysis (WGCNA). LncRNA/mRNA regulatory networks were constructed based on the WGCNA and subjected to functional enrichment analysis.Results: In total, 3,355 mRNAs and 999 lncRNAs were identified as differentially expressed genes between patients with high and low BMD. The WGCNA yielded three gene modules, including 26 lncRNAs and 55 mRNAs as hub genes in the blue module, 36 lncRNAs and 31 mRNAs as hub genes in the turquoise module, and 56 mRNAs and 30 lncRNAs as hub genes in the brown module. JUN and ACSL5 were subsequently identified in the modular gene network. After functional pathway enrichment, 40 lncRNAs and 16 mRNAs were found to be related to differences in BMD. All three modules were enriched in metabolic pathways. Finally, mRNA/lncRNA/pathway networks were constructed using the identified regulatory networks of lncRNAs/mRNAs and pathway enrichment relationships.Conclusion: The mRNAs and lncRNAs identified in this WGCNA could be novel clinical targets in the diagnosis and management of osteoporosis. Our findings may help elucidate the complex interactions between transcripts and non-coding RNAs and provide novel perspectives on the regulatory mechanisms of osteoporosis.
Highlights
Osteoporosis is a systemic disease of the musculoskeletal system
According to the National Health and Nutrition Examination Survey III, there are more than 9.9 million patients with osteoporosis in the United States of America, and 1.5 million patients suffer from osteoporotic fractures each year (Sahni et al, 2009)
With an fold change (FC) cutoff value >1.2 and p < 0.05, 3,355 messenger RNA (mRNA) (Figures 2A,C) and 999 long non-coding RNAs (lncRNAs) (Figures 2B,D) were identified as differentially expressed between patients with high and low hip bone mineral density (BMD); these were selected as candidate genes for subsequent Weighted gene co-expression network analysis (WGCNA)
Summary
Osteoporosis is a systemic disease of the musculoskeletal system. According to the National Health and Nutrition Examination Survey III, there are more than 9.9 million patients with osteoporosis in the United States of America, and 1.5 million patients suffer from osteoporotic fractures each year (Sahni et al, 2009). Affected by many factors, such as menopause, women are especially susceptible to osteoporosis (Baccaro et al, 2015). A large-scale epidemiological survey in 2006 showed that among people over 50 years old, the prevalence of osteoporosis in men was 14.4%, whereas that in women was as high as 20.7%(Chen et al, 2016). Osteoporosis is a highly heritable skeletal muscle disease. In this study, we aimed to clarify the transcriptional regulation and heritability underlying the onset of osteoporosis
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