Conclusion
Jun plays a crucial role in OA development and causes senescence by destabilizing chromatin in chondrocytes. These findings provide new insights into OA progression and suggest promising therapeutic targets.
Methods
Bioinformatic methods were used to screen key genes. Immunohistochemistry and the quantitative reverse transcription polymerase chain reaction were used to evaluate gene expression. RNA intervention experiments were performed to explore the functions of key genes.
Objective
Osteoarthritis (OA) is the most common degenerative joint disease leading to disability worldwide. Cellular senescence is considered to be a fundamental pathogenic mechanism in the development of OA and has attracted increasing attention. However, regulatory mechanisms underlying chondrocyte senescence in OA remain unclear.
Results
We used 494 aging-associated genes provided by the Aging Atlas to identify the co-expression modules associated with age and OA. Thirty age-associated differentially expressed genes (ASDEGs) were identified. Using cytoHubba in Cytoscape, we identified Jun as the hub-ASDEG for OA chondrocytes. We confirmed the downregulation of Jun in OA rats and senescent chondrocytes by immunohistochemistry and quantitative reverse transcription polymerase chain reaction, respectively. Inhibition of proliferation and accelerated senescence were observed in chondrocytes treated with siRNA against Jun. Mechanistically, we observed micronuclei formation and reduced expression of H3K9me3 and heterochromatin protein 1gamma in siRNA-Jun-treated chondrocytes, indicating that destabilization of chromatin occurred during this treatment.