Abstract
Sex differences have been suggested to play critical roles in the pathophysiology of osteoarthritis (OA), resulting in sex-specific prevalence and incidence. However, their roles in the development of OA remain largely unknown. The aim of this study was to screen out key genes and pathways mediating biological differences between OA females after menopause and OA males. First, the gene expression data of GSE36700 and GSE55457 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between sexes were identified using R software, respectively. The overlapping DEGs were obtained. Then, protein-protein interactive (PPI) network was constructed to further analyze interactions between the overlapping DEGs. Finally, enrichment analyses were separately performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes tools. In our results, a total of 278 overlapping DEGs were identified between OA females after menopause and OA males, including 219 upregulated and 59 downregulated genes. In the PPI network, seven hub genes were identified, including EGF, ERBB2, CDC42, PIK3R2, LCK, CBL, and STAT1. Functional enrichment analysis revealed that these genes were mainly enriched in PI3K-Akt signaling pathway, osteoclast differentiation, and focal adhesion. In conclusion, the results in the current study suggest that pathways of PI3K-Akt, osteoclast differentiation, and focal adhesion may play important roles in the development of OA females after menopause. EGFR, ERBB2, CDC42, and STAT1 may be key genes related to OA progression in postmenopausal women and may be promising therapeutic targets for OA.
Highlights
Osteoarthritis (OA), the most common musculoskeletal disorder, leads to functional disability and loss in quality of life
Our study, for the first time, identified key genes and pathways in synovial membrane of OA females after menopause compared to OA males using bioinformatics analysis
We performed an integrated bioinformatics analysis using two Gene Expression Omnibus (GEO) datasets of gene expression profiles to identify the biological mechanisms involved in the pathogenesis of sexes differences in OA
Summary
Osteoarthritis (OA), the most common musculoskeletal disorder, leads to functional disability and loss in quality of life It affects women after menopause 2-3 times often than men [1]; worldwide disease estimates show that approximately 18% of women and 6% of men at the age of 60 years or older suffer from OA [2]. It is characterized by cartilage degradation, synovial inflammation, subchondral bone sclerosis, and chronic pain [3, 4]. It is urgent to explore potential biomarkers and therapeutic targets for OA
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