Significantly dysregulated genes in osteoarthritic labrum cells identified through gene expression profiling

Abstract

The aim of the present study was to explore the molecular basis and identify significant genetic alterations in acetabular labrum cells associated with osteoarthritis (oA). Gene expression data of osteoarthritic and normal human labrum cells were downloaded from a public database and reanalyzed. Significant differentially expressed genes (DEGs) were acquired by performing a thorough analysis of microarray data between the oA acetabular labrum cells and control cells. Key genes in oA labrum cells were revealed by a combination of weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPi) analysis. Literature mining and drug screening were further performed for these key genes. i n total, 141 D E G S between o A and normal labrum cells were identified. In addition, W G C N A and PPI analysis identified 23 DEGs as key genes in the OA labrum. A l l the key genes were significantly downregulated in OA labrum cells and were grouped into two different W G C N A - P P I common subnetworks. Kinase insert domain receptor (KDR), CD34, cadherin 5 (CDH5), Fms related tyrosine kinase 1 (FLT1) and asporin were hub nodes i n the PPi network of D E G S . These key genes were significantly enriched i n functional clusters of transforming growth factor, alkaline phosphatase, bone morphogenic protein and extracellular matrix. Drug screening analysis identified several drugs targeting the key genes, including arachidonic acid, yohimbic acid and mimosine. The results of the present study indicate that the changes of FLT1, KDR, CD34 and CDH5 in acetabular labrum cells may be involved in the pathogenesis of oA and could serve as biomarkers and therapeutic targets of o A . Additionally, arachidonic acid, yohimbic acid and mimosine may act as potential drugs for o A .