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

Tiina Lehtola, Elina Nummenmaa, Lauri Tuure, Mari Hämäläinen, Riina M. Nieminen, Teemu Moilanen, Antti Pemmari, Eeva Moilanen

Research output: Contribution to journalArticleScientificpeer-review

Abstract

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.

Original languageEnglish
Article number3880
Number of pages12
JournalInternational Journal of Molecular Sciences
Volume23
Issue number7
DOIs
Publication statusPublished - Mar 2022
Publication typeA1 Journal article-refereed

Keywords

  • chondrocyte
  • dexamethasone
  • inflammation
  • MKP‐1
  • MMP‐13
  • osteoarthritis

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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