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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. In total, 141 DEGs between OA and normal labrum cells were identified. In addition, WGCNA and PPI analysis identified 23 DEGs as key genes in the OA labrum. All the key genes were significantly downregulated in OA labrum cells and were grouped into two different WGCNA?PPI common subnetworks. Kinase insert domain receptor (KDR), CD34, cadherin 5 (CDH5), Fms related tyrosine kinase 1 (FLT1) and asporin were hub nodes in the PPI network of DEGs. These key genes were significantly enriched in 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 OA. Additionally, arachidonic acid, yohimbic acid and mimosine may act as potential drugs for OA.

SUBMITTER: Wang S

PROVIDER: S-EPMC6625433 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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

Wang Shuai S Jiang Chunyan C Zhang Kefeng K

Molecular medicine reports 20190618 2

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 ...[more]

PMID: 31257478

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Project description:Aim:Osteoarthritis (OA) is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control the expression of genes and are likely to regulate the OA transcriptome. We performed integrative genomic analyses to define methylation-gene expression relationships in osteoarthritic cartilage. Patients and Methods:Genome-wide DNA methylation profiling of articular cartilage from five patients with OA of the knee and five healthy controls was conducted using the Illumina Infinium HumanMethylation450 BeadChip (Illumina, San Diego, California). Other independent genome-wide mRNA expression profiles of articular cartilage from three patients with OA and three healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Integrative pathway enrichment analysis of DNA methylation and mRNA expression profiles was performed using integrated analysis of cross-platform microarray and pathway software. Gene ontology (GO) analysis was conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Results:We identified 1265 differentially methylated genes, of which 145 are associated with significant changes in gene expression, such as DLX5, NCOR2 and AXIN2 (all p-values of both DNA methylation and mRNA expression < 0.05). Pathway enrichment analysis identified 26 OA-associated pathways, such as mitogen-activated protein kinase (MAPK) signalling pathway (p = 6.25 × 10-4), phosphatidylinositol (PI) signalling system (p = 4.38 × 10-3), hypoxia-inducible factor 1 (HIF-1) signalling pathway (p = 8.63 × 10-3 pantothenate and coenzyme A (CoA) biosynthesis (p = 0.017), ErbB signalling pathway (p = 0.024), inositol phosphate (IP) metabolism (p = 0.025), and calcium signalling pathway (p = 0.032). Conclusion:We identified a group of genes and biological pathwayswhich were significantly different in both DNA methylation and mRNA expression profiles between patients with OA and controls. These results may provide new clues for clarifying the mechanisms involved in the development of OA.Cite this article: A. He, Y. Ning, Y. Wen, Y. Cai, K. Xu, Y. Cai, J. Han, L. Liu, Y. Du, X. Liang, P. Li, Q. Fan, J. Hao, X. Wang, X. Guo, T. Ma, F. Zhang. Use of integrative epigenetic and mRNA expression analyses to identify significantly changed genes and functional pathways in osteoarthritic cartilage. Bone Joint Res 2018;7:343-350. DOI: 10.1302/2046-3758.75.BJR-2017-0284.R1.

Dataset Information

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

Publications

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

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