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Feprazone Mitigates IL-1β-Induced Cellular Senescence in Chondrocytes
[Image: see text] 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 wi...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047674/ https://www.ncbi.nlm.nih.gov/pubmed/33869924 http://dx.doi.org/10.1021/acsomega.0c06066 |
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author | Huang, Zhusong Lan, Jinfu Gao, Xi |
author_facet | Huang, Zhusong Lan, Jinfu Gao, Xi |
author_sort | Huang, Zhusong |
collection | PubMed |
description | [Image: see text] 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. |
format | Online Article Text |
id | pubmed-8047674 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-80476742021-04-16 Feprazone Mitigates IL-1β-Induced Cellular Senescence in Chondrocytes Huang, Zhusong Lan, Jinfu Gao, Xi ACS Omega [Image: see text] 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. American Chemical Society 2021-03-31 /pmc/articles/PMC8047674/ /pubmed/33869924 http://dx.doi.org/10.1021/acsomega.0c06066 Text en © 2021 The Authors. Published by American Chemical Society Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Huang, Zhusong Lan, Jinfu Gao, Xi Feprazone Mitigates IL-1β-Induced Cellular Senescence in Chondrocytes |
title | Feprazone Mitigates IL-1β-Induced Cellular Senescence
in Chondrocytes |
title_full | Feprazone Mitigates IL-1β-Induced Cellular Senescence
in Chondrocytes |
title_fullStr | Feprazone Mitigates IL-1β-Induced Cellular Senescence
in Chondrocytes |
title_full_unstemmed | Feprazone Mitigates IL-1β-Induced Cellular Senescence
in Chondrocytes |
title_short | Feprazone Mitigates IL-1β-Induced Cellular Senescence
in Chondrocytes |
title_sort | feprazone mitigates il-1β-induced cellular senescence
in chondrocytes |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047674/ https://www.ncbi.nlm.nih.gov/pubmed/33869924 http://dx.doi.org/10.1021/acsomega.0c06066 |
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