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Identification and validation of hub genes and potential drugs involved in osteoarthritis through bioinformatics

Wenbo Xu1, Xuyao Wang2, Donghui Liu3

  • 1The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Frontiers in Genetics
|February 27, 2023
PubMed

Insights

Researchers identified key genes (EGR1, JUN, MYC, FOSL1, FOSL2) involved in osteoarthritis (OA) synovium development using bioinformatics. These findings support Etanercept and Iguratimod as potential novel OA drugs.

Area of Science:

  • Molecular Biology
  • Genetics
  • Rheumatology

Background:

  • Osteoarthritis (OA) is a prevalent degenerative joint disease with limited targeted therapies.
  • Synovitis is a critical pathological process in OA pathogenesis.
  • Identifying key molecular players in OA synovium is crucial for therapeutic development.

Purpose of the Study:

  • To identify and analyze hub genes and regulatory networks in OA synovial tissue using bioinformatics.
  • To provide a theoretical basis for developing novel therapeutic drugs for OA.
  • To investigate the correlation of hub genes with ferroptosis and pyroptosis in OA.

Main Methods:

  • Analysis of gene expression datasets from OA synovial tissue.
  • Screening of differentially expressed genes (DEGs) and hub genes via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment.
  • Protein-protein interaction (PPI) network analysis and ceRNA regulatory network construction.
  • Validation of hub gene expression using RT-qPCR and ELISA.

Main Results:

  • 161 common DEGs were identified, with 8 selected as hub genes.
  • Significant correlations were found between hub gene expression and ferroptosis/pyroptosis.
  • A ceRNA network involving 24 miRNAs and 69 lncRNAs was constructed.
  • EGR1, JUN, MYC, FOSL1, and FOSL2 were validated as key hub genes.
  • Etanercept and Iguratimod reduced MMP-13 and ADAMTS5 secretion in fibroblast-like synoviocytes.

Conclusions:

  • EGR1, JUN, MYC, FOSL1, and FOSL2 are identified as critical hub genes in OA development.
  • The identified hub genes and networks offer insights into OA pathogenesis.
  • Etanercept and Iguratimod show potential as novel therapeutic agents for osteoarthritis.
Keywords:
GEObioinformatics analysisferroptosishub genesosteoarthritispyroptosis

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