Integrated Analysis of Transcriptome Changes in Osteoarthritis: Gene Expression, Pathways and Alternative Splicing

Area of Science:

• Molecular biology
• Genomics
• Biochemistry

Background:

• Osteoarthritis (OA) is a prevalent joint disease causing cartilage degeneration and bone remodeling, leading to pain and functional loss.
• Current treatments for OA are limited, with joint replacement being the primary option.
• The exact molecular mechanisms driving OA pathogenesis remain largely unknown.

Purpose of the Study:

• To investigate the molecular changes at the transcriptome level in osteoarthritis (OA) knee cartilage.
• To identify differential gene expression, alternative splicing events, and affected molecular pathways in OA.

Main Methods:

• RNA sequencing (RNA-seq) data analysis of OA knee cartilage.
• Differential gene expression analysis.
• Gene Set Enrichment Analysis (GSEA).
• Alternative splicing event analysis.

Main Results:

• Identified 457 differentially expressed genes (266 up-regulated, 191 down-regulated) in OA cartilage.
• GSEA revealed down-regulated pathways in translation, transcription, immunity, PI3K/AKT, and circadian rhythms, alongside disturbed extracellular matrix (ECM) and collagen pathways.
• Detected 442 differential alternative splicing events in 284 genes, with TIA1 identified as a key regulator, particularly affecting ECM and splicing-related genes.

Conclusions:

• The study provides novel insights into the molecular etiology of osteoarthritis.
• Identified molecular signatures and regulatory mechanisms offer potential targets for developing more effective OA interventions.