Comprehensive Bioinformatics Analysis Reveals Associations between the DNA Damage Response and Osteoarthritis

DNA damage in chondrocytes has been found to be associated with osteoarthritis (OA) and could be a primary pathological mechanism of the disease. Here, we performed transcriptomic analysis of human chondrocytes using existing RNA-seq datasets to characterize DNA damage repair pathway alterations associated with OA status.

We collected 9 public RNA-seq datasets of cartilage samples in the Gene Expression Omnibus from 57 OA patients and 35 non-OA controls. We identified differentially expressed genes (DEGs), examined enriched pathways, and predicted regulatory networks of the DNA damage response (DDR) in OA by comparing RNA-seq data from OA and non-OA chondrocytes. Furthermore, we evaluated the potential associations between DDR-related gene signatures and OA status.

We identified 490 upregulated and 350 downregulated DEGs in OA. The upregulated DEGs are significantly enriched in DDR pathways, including the Fanconi anemia, mismatch repair, and base excision repair pathways. A total of 10 significant DDR downstream pathways were enriched and upregulated in OA, including DNA replication, DNA repair, and cell cycle pathways in relation to the DDR. Finally, we identified 9 core genes for DNA damage repair in OA (DDR-OA genes) as potential targets for OA biomarkers. Three of these genes are known to be associated with both DDR processes and OA pathology.

Elevated expression of DDR-related genes and enhanced activity of DDR signaling pathways were observed in conjunction with OA onset and progression. Our computational analysis prioritizes identified DDR-OA genes as high-confidence candidates for further experimental investigation.