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Wnt/β-catenin signaling may induce senescence of chondrocytes in osteoarthritis

Osteoarthritis (OA) is an autoimmune disease associated with increasing age. Typically, chondrocyte senescence is believed to serve an important role in the development and progression of OA. However, the specific mechanisms underlying chondrocyte senescence have not been fully addressed. The presen...

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Autores principales: Li, Weijun, Xiong, Yan, Chen, Weiping, Wu, Lidong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401843/
https://www.ncbi.nlm.nih.gov/pubmed/32765756
http://dx.doi.org/10.3892/etm.2020.9022
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author Li, Weijun
Xiong, Yan
Chen, Weiping
Wu, Lidong
author_facet Li, Weijun
Xiong, Yan
Chen, Weiping
Wu, Lidong
author_sort Li, Weijun
collection PubMed
description Osteoarthritis (OA) is an autoimmune disease associated with increasing age. Typically, chondrocyte senescence is believed to serve an important role in the development and progression of OA. However, the specific mechanisms underlying chondrocyte senescence have not been fully addressed. The present study hypothesized that the Wnt/β-catenin signaling may represent a major regulator of chondrocyte senescence. In addition, the acetylated levels of p53 and sirtuin-1 (SIRT-1) were examined as putative markers for chondrocyte senescence, since activation of p53 is considered an important step in the regulation of senescence. The Wnt/β-catenin signaling pathway was activated using LiCl and inhibited using the Wnt signaling pathway inhibitor, dickkopf-1 (DKK1) in order to evaluate the role of this pathway in the development of OA. Senescent cells were detected using the senescence-associated indicator acidic senescence-associated β-galactosidase (SA-β-gal). The effects of p53 and p16 on chondrocyte senescence were assessed via activation of Wnt/β-catenin signaling using Wnt-1. In addition, β-catenin was transfected into chondrocytes to induce activation of the Wnt/β-catenin signaling pathway. Finally, a rabbit model of OA was used to assess whether the observed effects on the Wnt/β-catenin signaling pathway and the induction of chondrocyte senescence were perpetuated. Activation of Wnt/β-catenin signaling increased the expression levels of SA-β-gal, p53, p16 and acetylated p53. Transfection of β-catenin in chondrocytes increased the expression levels of acetylated p53 and decreased the expression levels of SIRT-1, which in turn deacetylated p53 and modulated its activity. Finally, the role of the Wnt/β-catenin signaling pathway was confirmed in the development of OA using a rabbit model with this condition. The present study suggested that activation of the Wnt/β-catenin signaling pathway promoted chondrocyte senescence, through downregulation of SIRT-1 and increased the expression of acetylated p53.
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spelling pubmed-74018432020-08-05 Wnt/β-catenin signaling may induce senescence of chondrocytes in osteoarthritis Li, Weijun Xiong, Yan Chen, Weiping Wu, Lidong Exp Ther Med Articles Osteoarthritis (OA) is an autoimmune disease associated with increasing age. Typically, chondrocyte senescence is believed to serve an important role in the development and progression of OA. However, the specific mechanisms underlying chondrocyte senescence have not been fully addressed. The present study hypothesized that the Wnt/β-catenin signaling may represent a major regulator of chondrocyte senescence. In addition, the acetylated levels of p53 and sirtuin-1 (SIRT-1) were examined as putative markers for chondrocyte senescence, since activation of p53 is considered an important step in the regulation of senescence. The Wnt/β-catenin signaling pathway was activated using LiCl and inhibited using the Wnt signaling pathway inhibitor, dickkopf-1 (DKK1) in order to evaluate the role of this pathway in the development of OA. Senescent cells were detected using the senescence-associated indicator acidic senescence-associated β-galactosidase (SA-β-gal). The effects of p53 and p16 on chondrocyte senescence were assessed via activation of Wnt/β-catenin signaling using Wnt-1. In addition, β-catenin was transfected into chondrocytes to induce activation of the Wnt/β-catenin signaling pathway. Finally, a rabbit model of OA was used to assess whether the observed effects on the Wnt/β-catenin signaling pathway and the induction of chondrocyte senescence were perpetuated. Activation of Wnt/β-catenin signaling increased the expression levels of SA-β-gal, p53, p16 and acetylated p53. Transfection of β-catenin in chondrocytes increased the expression levels of acetylated p53 and decreased the expression levels of SIRT-1, which in turn deacetylated p53 and modulated its activity. Finally, the role of the Wnt/β-catenin signaling pathway was confirmed in the development of OA using a rabbit model with this condition. The present study suggested that activation of the Wnt/β-catenin signaling pathway promoted chondrocyte senescence, through downregulation of SIRT-1 and increased the expression of acetylated p53. D.A. Spandidos 2020-09 2020-07-17 /pmc/articles/PMC7401843/ /pubmed/32765756 http://dx.doi.org/10.3892/etm.2020.9022 Text en Copyright: © Li 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
Li, Weijun
Xiong, Yan
Chen, Weiping
Wu, Lidong
Wnt/β-catenin signaling may induce senescence of chondrocytes in osteoarthritis
title Wnt/β-catenin signaling may induce senescence of chondrocytes in osteoarthritis
title_full Wnt/β-catenin signaling may induce senescence of chondrocytes in osteoarthritis
title_fullStr Wnt/β-catenin signaling may induce senescence of chondrocytes in osteoarthritis
title_full_unstemmed Wnt/β-catenin signaling may induce senescence of chondrocytes in osteoarthritis
title_short Wnt/β-catenin signaling may induce senescence of chondrocytes in osteoarthritis
title_sort wnt/β-catenin signaling may induce senescence of chondrocytes in osteoarthritis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401843/
https://www.ncbi.nlm.nih.gov/pubmed/32765756
http://dx.doi.org/10.3892/etm.2020.9022
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