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Apremilast prevents IL-17-induced cellular senescence in ATDC5 chondrocytes mediated by SIRT1

Osteoarthritis is the most prevalent joint degenerative disease and has been considered a major cause of severe joint pain and physical disability in the elderly. The chondrocyte is the only cell type found in articular cartilage and chondrocyte senescence plays a pivotal role in the pathogenesis of...

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Autores principales: Wang, Benlong, Sun, Wei, Bi, Kunwei, Li, Yong, Li, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834959/
https://www.ncbi.nlm.nih.gov/pubmed/33448323
http://dx.doi.org/10.3892/ijmm.2021.4845
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author Wang, Benlong
Sun, Wei
Bi, Kunwei
Li, Yong
Li, Feng
author_facet Wang, Benlong
Sun, Wei
Bi, Kunwei
Li, Yong
Li, Feng
author_sort Wang, Benlong
collection PubMed
description Osteoarthritis is the most prevalent joint degenerative disease and has been considered a major cause of severe joint pain and physical disability in the elderly. The chondrocyte is the only cell type found in articular cartilage and chondrocyte senescence plays a pivotal role in the pathogenesis of osteoarthritis. Apremilast is an oral PDE4 inhibitor and has been used for the treatment of patients with active psoriatic arthritis. In the present study, the biological function of apremilast was examined in an interleukin (IL)-17-treated chondrocyte model. Expression levels of target genes and proteins were measured using reverse transcription-quantitative PCR, ELISA, and western blotting, respectively. ROS levels in chondrocytes were examined using the fluorescent dye DCFH-DA. Cellular senescence was determined using senescence-associated-β-galactosidase staining. The profile of cell cycle phases was analyzed via flow cytometry. It was revealed that treatment with apremilast reduced the expression of IL-1β, MCP-1, and the production of ROS. SA-β-gal staining results indicated that the presence of apremilast suppressed IL-17-induced cellular senescence. Furthermore, apremilast prevented IL-17-induced G0/G1 phase cell cycle arrest. In addition, it was demonstrated that apremilast suppressed IL-17-induced expression of p21 and PAI-1. Notably, the silencing of sirtuin 1 (SIRT1) abolished the protective effect of apremilast against IL-17-induced cellular senescence, suggesting that the action of apremilast in chondrocytes is dependent on SIRT1. In conclusion, the present results revealed that apremilast exerted a beneficial effect, thereby protecting chondrocytes from senescence induced by IL-17.
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spelling pubmed-78349592021-02-05 Apremilast prevents IL-17-induced cellular senescence in ATDC5 chondrocytes mediated by SIRT1 Wang, Benlong Sun, Wei Bi, Kunwei Li, Yong Li, Feng Int J Mol Med Articles Osteoarthritis is the most prevalent joint degenerative disease and has been considered a major cause of severe joint pain and physical disability in the elderly. The chondrocyte is the only cell type found in articular cartilage and chondrocyte senescence plays a pivotal role in the pathogenesis of osteoarthritis. Apremilast is an oral PDE4 inhibitor and has been used for the treatment of patients with active psoriatic arthritis. In the present study, the biological function of apremilast was examined in an interleukin (IL)-17-treated chondrocyte model. Expression levels of target genes and proteins were measured using reverse transcription-quantitative PCR, ELISA, and western blotting, respectively. ROS levels in chondrocytes were examined using the fluorescent dye DCFH-DA. Cellular senescence was determined using senescence-associated-β-galactosidase staining. The profile of cell cycle phases was analyzed via flow cytometry. It was revealed that treatment with apremilast reduced the expression of IL-1β, MCP-1, and the production of ROS. SA-β-gal staining results indicated that the presence of apremilast suppressed IL-17-induced cellular senescence. Furthermore, apremilast prevented IL-17-induced G0/G1 phase cell cycle arrest. In addition, it was demonstrated that apremilast suppressed IL-17-induced expression of p21 and PAI-1. Notably, the silencing of sirtuin 1 (SIRT1) abolished the protective effect of apremilast against IL-17-induced cellular senescence, suggesting that the action of apremilast in chondrocytes is dependent on SIRT1. In conclusion, the present results revealed that apremilast exerted a beneficial effect, thereby protecting chondrocytes from senescence induced by IL-17. D.A. Spandidos 2021-03 2021-01-05 /pmc/articles/PMC7834959/ /pubmed/33448323 http://dx.doi.org/10.3892/ijmm.2021.4845 Text en Copyright: © Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Wang, Benlong
Sun, Wei
Bi, Kunwei
Li, Yong
Li, Feng
Apremilast prevents IL-17-induced cellular senescence in ATDC5 chondrocytes mediated by SIRT1
title Apremilast prevents IL-17-induced cellular senescence in ATDC5 chondrocytes mediated by SIRT1
title_full Apremilast prevents IL-17-induced cellular senescence in ATDC5 chondrocytes mediated by SIRT1
title_fullStr Apremilast prevents IL-17-induced cellular senescence in ATDC5 chondrocytes mediated by SIRT1
title_full_unstemmed Apremilast prevents IL-17-induced cellular senescence in ATDC5 chondrocytes mediated by SIRT1
title_short Apremilast prevents IL-17-induced cellular senescence in ATDC5 chondrocytes mediated by SIRT1
title_sort apremilast prevents il-17-induced cellular senescence in atdc5 chondrocytes mediated by sirt1
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834959/
https://www.ncbi.nlm.nih.gov/pubmed/33448323
http://dx.doi.org/10.3892/ijmm.2021.4845
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