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Sex Differences in Osteoarthritis Pathogenesis: A Comprehensive Study Based on Bioinformatics.

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Osteoarthritis (OA) pathogenesis differs between males and females, with distinct gene expression patterns and signaling pathways identified. These sex-specific differentially expressed genes (DEGs) offer potential therapeutic targets and prognosis markers for OA.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Bioinformatics

Background:

  • Osteoarthritis (OA) is a prevalent degenerative joint disease affecting the elderly worldwide.
  • The sex-specific mechanisms underlying OA pathogenesis remain largely unexplored.
  • Understanding these differences is crucial for developing targeted OA treatments.

Purpose of the Study:

  • To investigate sex-specific differentially expressed genes (DEGs) in osteoarthritis.
  • To explore distinct signaling pathways involved in male and female OA.
  • To identify potential sex-dependent biomarkers and therapeutic targets for OA.

Main Methods:

  • Utilized Gene Expression Omnibus (GEO) datasets (GSE55457, GSE55584, GSE12021) for DEG analysis.
  • Performed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analysis using DAVID.
  • Constructed protein-protein interaction networks with Cytoscape and validated hub genes via qRT-PCR.

Main Results:

  • Identified 4 co-upregulated and 10 co-downregulated genes between sexes.
  • Discovered sex-specific enriched pathways in OA pathogenesis.
  • Identified key hub genes: BCL2L1, EEF1A1, EEF2, HNRNPD, PABPN1 in males; EEF2, EEF1A1, RPL37A, FN1 in females.
  • Validated differential gene expression in male and female OA patients via qRT-PCR.

Conclusions:

  • Differentially expressed genes suggest sex-dependent mechanisms in OA progression.
  • Identified genes serve as potential prognostic markers and therapeutic targets for OA in a sex-specific manner.
  • OA pathogenesis exhibits significant sex-dependent characteristics.