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- Title
Dexamethasone Attenuates the Expression of MMP-13 in Chondrocytes through MKP-1.
- Authors
Lehtola, Tiina; Nummenmaa, Elina; Tuure, Lauri; Hämäläinen, Mari; Nieminen, Riina M.; Moilanen, Teemu; Pemmari, Antti; Moilanen, Eeva
- 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.
- Subjects
MATRIX metalloproteinases; CARTILAGE cells; DEXAMETHASONE; MITOGEN-activated protein kinases
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 7, p3880
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23073880