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Identification of transcription factors responsible for dysregulated networks in human osteoarthritis cartilage by global gene expression analysis

ABSTRACT: Identification of transcription factors responsible for dysregulated networks in human osteoarthritis cartilage by global gene expression analysis

PROVIDER: PRJNA454873 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7107490.fastq.gz	Fastqsanger.gz
	SRR7107500.fastq.gz	Fastqsanger.gz
	SRR7107510.fastq.gz	Fastqsanger.gz
	SRR7107481.fastq.gz	Fastqsanger.gz
	SRR7107491.fastq.gz	Fastqsanger.gz

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Identification of transcription factors responsible for dysregulated networks in human osteoarthritis cartilage by global gene expression analysis

Project description:Objective:Osteoarthritis (OA) is the most prevalent joint disease. As disease-modifying therapies are not available, novel therapeutic targets need to be discovered and prioritized for their importance in mediating the abnormal phenotype of cells in OA-affected joints. Here, we generated a genome-wide molecular profile of OA to elucidate regulatory mechanisms of OA pathogenesis and to identify possible therapeutic targets using integrative analysis of mRNA-sequencing data obtained from human knee cartilage. Methods:RNA-sequencing (RNA-seq) was performed on 18 normal and 20 OA human knee cartilage tissues. RNA-seq datasets were analysed to identify genes, pathways and regulatory networks that were dysregulated in OA. Results:RNA-seq data analysis revealed 1332 differentially expressed (DE) genes between OA and non-OA samples, including known and novel transcription factors (TFs). Pathway analysis identified 15 significantly perturbed pathways in OA with ECM-related, PI3K-Akt, HIF-1, FoxO and circadian rhythm pathways being the most significantly dysregulated. We selected differentially expressed TFs that are enriched for regulating DE genes in OA and prioritized these transcription factors by creating a cartilage-specific interaction subnetwork. This analysis revealed 8 TFs, including JUN, EGR1, JUND, FOSL2, MYC, KLF4, RELA, and FOS that both target large numbers of dysregulated genes in OA and are themselves suppressed in OA. Conclusion:We identified a novel subnetwork of dysregulated TFs that represent new mediators of abnormal gene expression and promising therapeutic targets in OA.

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Dysregulated gene expression in human osteoarthritis cartilage

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Osteoarthritis RNA Sequencing from ground cartilage samples

Project description:Osteoarthritis (OA) is the most prevalent joint disease with the typifying feature being the progressive degradation of articular cartilage during disease progression. In this study we used whole transcriptome RNA-seq as a tool to compare gene expression changes between age-matched osteoarthritic human hip OA cartilage (n=10) compared to control (neck of femur fracture) cartilage (n=6) [GSE107308]. All cartilage was from patients undergoing acetabulofemoral joint replacement. Cartilage RNA was isolated from cartilage within 2 hr of joint replacement surgery, mRNA was polyA purified and transcript expression was analysed using 78-base paired-end sequencing generating on average 28 million reads/sample sequencing. The data shows excellent correlation with our previous microarray data but identifies significantly more differentially expressed transcripts plus novel transcript variants, several of which have been validated by real-time qPCR. Our work sheds further light on chondrocyte transcriptome expression and highlights gene expression changes and novel transcripts potentially important in osteoarthritis progression

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