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Huang Z, Lan J, Gao X. Feprazone Mitigates IL-1β-Induced Cellular Senescence in Chondrocytes. ACS Omega. 2021;6(14):9442-9448doi: 10.1021/acsomega.0c06066.
Huang, Z., Lan, J., & Gao, X. (2021). Feprazone Mitigates IL-1β-Induced Cellular Senescence in Chondrocytes. ACS omega, 6(14), 9442-9448. https://doi.org/10.1021/acsomega.0c06066
Huang, Zhusong, et al. "Feprazone Mitigates IL-1β-Induced Cellular Senescence in Chondrocytes." ACS omega vol. 6,14 (2021): 9442-9448. doi: https://doi.org/10.1021/acsomega.0c06066
Huang Z, Lan J, Gao X. Feprazone Mitigates IL-1β-Induced Cellular Senescence in Chondrocytes. ACS Omega. 2021 Mar 31;6(14):9442-9448. doi: 10.1021/acsomega.0c06066. eCollection 2021 Apr 13. PMID: 33869924; PMCID: PMC8047674.
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ACS Omega. 2021 Mar 31;6(14):9442-9448. doi: 10.1021/acsomega.0c06066. eCollection 2021 Apr 13.

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

ACS omega

Zhusong Huang, Jinfu Lan, Xi Gao

Affiliations

  1. Department of Orthopaedics, Fuzhou Second Hospital of Xiamen University, No. 47 Shangteng Road, Cangshan District, Fuzhou, Fujian 350007, China.

PMID: 33869924 PMCID: PMC8047674 DOI: 10.1021/acsomega.0c06066

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.

© 2021 The Authors. Published by American Chemical Society.

Conflict of interest statement

The authors declare no competing financial interest.

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