Celecoxib prevents tumor necrosis factor-α (TNF-α)-induced cellular senescence in human chondrocytes

Osteoarthritis (OA) is a cartilage degenerative disease commonly observed in the elderly population and significantly impacts the normal life of OA patients. It has been reported that the development of pathological cell senescence in chondrocytes is involved in the pathogenesis of OA. Celecoxib is a common non-steroidal anti-inflammatory drug, and it has been recently reported to exert therapeutic effects on OA. However, its underlying mechanism is still unclear. The present study intends to explore its mechanism and provide fundamental evidence for the application of Celecoxib in the treatment of clinical OA. Tumor necrosis factor-alpha (TNF-alpha) was utilized to establish an in vitro model of chondrocytes senescence. The elevated reactive oxygen species (ROS) generation, increased cell cycle arrest in G0/G1 phase, reduced telomerase activity, and upregulated senescence-associated beta-galactosidase (SA-beta-Gal) staining were all observed in TNF-alpha-treated chondrocytes, which were then dramatically reversed by 10 and 20 mu M Celecoxib. In addition, the upregulated DNA damage biomarkers, p-ATM, and p-CHK2, observed in TNF-alpha-treated chondrocytes were significantly downregulated by 10 and 20 mu M Celecoxib. Lastly, the expression level of p21 and p53 was greatly elevated in chondrocytes by stimulation with TNF-alpha which was then pronouncedly repressed by treatment with Celecoxib. Taken together, our data reveal that Celecoxib ameliorated TNF-alpha-induced cellular senescence in human chondrocytes.

Automated summary

Celecoxib alleviates TNF-α-induced cellular senescence in human chondrocytes by reducing ROS production, regulating the cell cycle, restoring telomerase activity, preventing DNA damage, and suppressing the expression of p21 and p53.