Feprazone Mitigates IL-1β-Induced Cellular Senescence in Chondrocytes

Abstract

The proinflammatory cytokine interleukin-1 β (IL-1β)-mediated cellular senescence in chondrocytes is involved in the development and pathological progression of osteoarthritis (OA). Feprazone, a nonsteroidal anti-inflammatory drug (NSAID) and a cyclooxygenase (COX) inhibitor, is widely used in clinics. This study aims to investigate whether Feprazone has a protective effect against IL-1β-induced cellular senescence in human chondrocytes. In this study, C-28/I2 chondrocytes were stimulated with IL-1β (10 ng/mL) in the presence or absence of Feprazone (10 and 20 μM). Cellular senescence was assessed using senescence-associated β-galactosidase (SA-β-Gal) staining. The cell cycle was examined using flow cytometry. Gene and protein expressions were determined with real-time polymerase chain reaction (PCR) and western blot analysis. We found that treatment with Feprazone ameliorated IL-1β-induced increase in cellular senescence. Feprazone increased telomerase activity and prevented cell cycle arrest in the G0/G1 phase. We also found that Feprazone reduced the expressions of plasminogen activator inhibitor-1 (PAI-1) and p21, two important regulators of cellular senescence. Additionally, treatment with Feprazone reduced the expressions of matrix metalloprotein (MMP-13) and a disintegrin-like and metalloproteinase with thrombospondin type-1 motif-5 (ADAMTS-5). Interestingly, Feprazone prevented the activation of nuclear factor kappa-B (NF-κB) by preventing nuclear translocation of NF-κB p65 and the luciferase activity of the NF-κB promoter. The results also show that Feprazone increased nuclear levels of nuclear factor erythroid 2-related factor-2 (Nrf2) and reduced the production of reactive oxygen species (ROS). Importantly, silencing of Nrf2 abolished the protective effects of Feprazone against IL-1β-induced NF-κB activation and cellular senescence. These findings shed light on the potential use of Feprazone in the treatment of OA based on a novel mechanism.

Secretory Factors from Calcium-Sensing Receptor-Activated SW872 Pre-Adipocytes Induce Cellular Senescence and A Mitochondrial Fragmentation-Mediated Inflammatory Response in HepG2 Cells

“…The process begins with an increase in cellular senescence markers such as SA-β-GAL and greater expression of pro-inflammatory cytokines and chemoattractants such as IL-1β and CCL2 [ 44 ]. In this context, the increased expression of IL-1β and CCL2 triggers the spread of inflammation and the attraction of immune cells, which eliminate senescent cells [ 14 , 44 , 45 ].…”

Microgel Encapsulated Nanoparticles for Intra-articular Disulfiram Delivery to Treat Osteoarthritis

“…The chondrocytes were seeded in 96-well plates, and after 24 h, the cells were treated with various concentrations of DSF for 2 h, then treated with IL-1β (10 ng/mL) for 24 h as described previously . Finally, 10 μL of the CCK8 reagent was added to the 96-well plates, and the plates were incubated at 37 °C for 2 h. The absorbance values were measured at 450 nm using a microplate reader (Thermo Fisher Scientific, USA).…”

Knockdown of lncRNA JPX suppresses IL‑1β‑stimulated injury in chondrocytes through modulating an miR‑25‑3p/PPID axis

“…C28/I2 cells were cultured in DMEM/F12 (Thermo Fisher Scientific, Inc.) supplemented with 10% FBS and 1% penicillin-streptomycin solution (Thermo Fisher Scientific, Inc.) and maintained in a humidified incubator supplied with 5% CO 2 at 37°C. To generate a model of OA, C28/I2 cells were treated with IL-1β recombinant protein (5, 10, and 20 ng/ml) for 24 h ( 37 ). C28/I2 cells without IL-1β treatment were used as the control.…”