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Dexamethasone Attenuates the Expression of MMP-13 in Chondrocytes through MKP-1

Mitogen-activated protein kinase phosphatase-1 (MKP-1) is upregulated in inflammation and reduces the activity of proinflammatory mitogen-activated protein kinases (MAP kinases) by dephosphorylation. MAP kinases are intracellular signaling pathways that mediate the cellular effects of proinflammator...

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Autores principales: Lehtola, Tiina, Nummenmaa, Elina, Tuure, Lauri, Hämäläinen, Mari, Nieminen, Riina M., Moilanen, Teemu, Pemmari, Antti, Moilanen, Eeva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998740/
https://www.ncbi.nlm.nih.gov/pubmed/35409238
http://dx.doi.org/10.3390/ijms23073880
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author Lehtola, Tiina
Nummenmaa, Elina
Tuure, Lauri
Hämäläinen, Mari
Nieminen, Riina M.
Moilanen, Teemu
Pemmari, Antti
Moilanen, Eeva
author_facet Lehtola, Tiina
Nummenmaa, Elina
Tuure, Lauri
Hämäläinen, Mari
Nieminen, Riina M.
Moilanen, Teemu
Pemmari, Antti
Moilanen, Eeva
author_sort Lehtola, Tiina
collection PubMed
description Mitogen-activated protein kinase phosphatase-1 (MKP-1) is upregulated in inflammation and reduces the activity of proinflammatory mitogen-activated protein kinases (MAP kinases) by dephosphorylation. MAP kinases are intracellular signaling pathways that mediate the cellular effects of proinflammatory cytokines. In the present study, we investigated the effects of the glucocorticoid dexamethasone on the expression of catabolic enzymes in chondrocytes and tested the hypothesis that these effects are mediated through MKP-1. Dexamethasone was found to significantly attenuate the expression of matrix metalloproteinase (MMP)-13 in human OA chondrocytes as well as in chondrocytes from MKP-1 WT mice, but not in chondrocytes from MKP-1 KO mice. Dexamethasone also increased the expression of MKP-1 in murine and human OA chondrocytes. Furthermore, p38 MAP kinase inhibitors significantly attenuated MMP-13 expression in human OA chondrocytes, while JNK MAP kinase inhibitors had no effect. The results indicate that the effect of dexamethasone on MMP-13 expression in chondrocytes was mediated by an MKP-1 and p38 MAP kinase-dependent manner. These findings, together with previous results, support the concept of MKP-1 as a protective factor in articular chondrocytes in inflammatory conditions and as a potential drug target to treat OA.
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spelling pubmed-89987402022-04-12 Dexamethasone Attenuates the Expression of MMP-13 in Chondrocytes through MKP-1 Lehtola, Tiina Nummenmaa, Elina Tuure, Lauri Hämäläinen, Mari Nieminen, Riina M. Moilanen, Teemu Pemmari, Antti Moilanen, Eeva Int J Mol Sci Article Mitogen-activated protein kinase phosphatase-1 (MKP-1) is upregulated in inflammation and reduces the activity of proinflammatory mitogen-activated protein kinases (MAP kinases) by dephosphorylation. MAP kinases are intracellular signaling pathways that mediate the cellular effects of proinflammatory cytokines. In the present study, we investigated the effects of the glucocorticoid dexamethasone on the expression of catabolic enzymes in chondrocytes and tested the hypothesis that these effects are mediated through MKP-1. Dexamethasone was found to significantly attenuate the expression of matrix metalloproteinase (MMP)-13 in human OA chondrocytes as well as in chondrocytes from MKP-1 WT mice, but not in chondrocytes from MKP-1 KO mice. Dexamethasone also increased the expression of MKP-1 in murine and human OA chondrocytes. Furthermore, p38 MAP kinase inhibitors significantly attenuated MMP-13 expression in human OA chondrocytes, while JNK MAP kinase inhibitors had no effect. The results indicate that the effect of dexamethasone on MMP-13 expression in chondrocytes was mediated by an MKP-1 and p38 MAP kinase-dependent manner. These findings, together with previous results, support the concept of MKP-1 as a protective factor in articular chondrocytes in inflammatory conditions and as a potential drug target to treat OA. MDPI 2022-03-31 /pmc/articles/PMC8998740/ /pubmed/35409238 http://dx.doi.org/10.3390/ijms23073880 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lehtola, Tiina
Nummenmaa, Elina
Tuure, Lauri
Hämäläinen, Mari
Nieminen, Riina M.
Moilanen, Teemu
Pemmari, Antti
Moilanen, Eeva
Dexamethasone Attenuates the Expression of MMP-13 in Chondrocytes through MKP-1
title Dexamethasone Attenuates the Expression of MMP-13 in Chondrocytes through MKP-1
title_full Dexamethasone Attenuates the Expression of MMP-13 in Chondrocytes through MKP-1
title_fullStr Dexamethasone Attenuates the Expression of MMP-13 in Chondrocytes through MKP-1
title_full_unstemmed Dexamethasone Attenuates the Expression of MMP-13 in Chondrocytes through MKP-1
title_short Dexamethasone Attenuates the Expression of MMP-13 in Chondrocytes through MKP-1
title_sort dexamethasone attenuates the expression of mmp-13 in chondrocytes through mkp-1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998740/
https://www.ncbi.nlm.nih.gov/pubmed/35409238
http://dx.doi.org/10.3390/ijms23073880
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