Cargando…

SERPINE2 Inhibits IL-1α-Induced MMP-13 Expression in Human Chondrocytes: Involvement of ERK/NF-κB/AP-1 Pathways

OBJECTIVES: Osteoarthritis (OA) is a chronic joint disease, characterized by a progressive loss of articular cartilage. During OA, proinflammatory cytokines, such as interleukin IL-1, induce the expression of matrix metalloproteinases (MMPs) in chondrocytes, contributing thus to the extracellular ma...

Descripción completa

Detalles Bibliográficos
Autores principales: Santoro, Anna, Conde, Javier, Scotece, Morena, Abella, Vanessa, Lois, Ana, Lopez, Veronica, Pino, Jesus, Gomez, Rodolfo, Gomez-Reino, Juan J., Gualillo, Oreste
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549255/
https://www.ncbi.nlm.nih.gov/pubmed/26305372
http://dx.doi.org/10.1371/journal.pone.0135979
_version_ 1782387286874259456
author Santoro, Anna
Conde, Javier
Scotece, Morena
Abella, Vanessa
Lois, Ana
Lopez, Veronica
Pino, Jesus
Gomez, Rodolfo
Gomez-Reino, Juan J.
Gualillo, Oreste
author_facet Santoro, Anna
Conde, Javier
Scotece, Morena
Abella, Vanessa
Lois, Ana
Lopez, Veronica
Pino, Jesus
Gomez, Rodolfo
Gomez-Reino, Juan J.
Gualillo, Oreste
author_sort Santoro, Anna
collection PubMed
description OBJECTIVES: Osteoarthritis (OA) is a chronic joint disease, characterized by a progressive loss of articular cartilage. During OA, proinflammatory cytokines, such as interleukin IL-1, induce the expression of matrix metalloproteinases (MMPs) in chondrocytes, contributing thus to the extracellular matrix (ECM) degradation. Members of Serpine family, including plasminogen activator inhibitors have been reported to participate in ECM regulation. The aim of this study was to assess the expression of serpin peptidase inhibitor clade E member 2 (SERPINE2), under basal conditions and in response to increasing doses of IL-1α, in human cultured chondrocytes. We also examined the effects of SERPINE2 on IL-1α-induced MMP-13 expression. For completeness, the signaling pathway involved in this process was also explored. METHODS: SERPINE2 mRNA and protein expression were evaluated by RT-qPCR and western blot analysis in human T/C-28a2 cell line and human primary chondrocytes. These cells were treated with human recombinant SERPINE2, alone or in combination with IL-1α. ERK 1/2, NFκB and AP-1 activation were assessed by western blot analysis. RESULTS: Human cultured chondrocytes express SERPINE2 in basal condition. This expression increased in response to IL-1α stimulation. In addition, recombinant SERPINE2 induced a clear inhibition of MMP-13 expression in IL-1α-stimulated chondrocytes. This inhibitory effect is likely regulated through a pathway involving ERK 1/2, NF-κB and AP-1. CONCLUSIONS: Taken together, these data demonstrate that SERPINE2 might prevent cartilage catabolism by inhibiting the expression of MMP-13, one of the most relevant collagenases, involved in cartilage breakdown in OA.
format Online
Article
Text
id pubmed-4549255
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-45492552015-09-01 SERPINE2 Inhibits IL-1α-Induced MMP-13 Expression in Human Chondrocytes: Involvement of ERK/NF-κB/AP-1 Pathways Santoro, Anna Conde, Javier Scotece, Morena Abella, Vanessa Lois, Ana Lopez, Veronica Pino, Jesus Gomez, Rodolfo Gomez-Reino, Juan J. Gualillo, Oreste PLoS One Research Article OBJECTIVES: Osteoarthritis (OA) is a chronic joint disease, characterized by a progressive loss of articular cartilage. During OA, proinflammatory cytokines, such as interleukin IL-1, induce the expression of matrix metalloproteinases (MMPs) in chondrocytes, contributing thus to the extracellular matrix (ECM) degradation. Members of Serpine family, including plasminogen activator inhibitors have been reported to participate in ECM regulation. The aim of this study was to assess the expression of serpin peptidase inhibitor clade E member 2 (SERPINE2), under basal conditions and in response to increasing doses of IL-1α, in human cultured chondrocytes. We also examined the effects of SERPINE2 on IL-1α-induced MMP-13 expression. For completeness, the signaling pathway involved in this process was also explored. METHODS: SERPINE2 mRNA and protein expression were evaluated by RT-qPCR and western blot analysis in human T/C-28a2 cell line and human primary chondrocytes. These cells were treated with human recombinant SERPINE2, alone or in combination with IL-1α. ERK 1/2, NFκB and AP-1 activation were assessed by western blot analysis. RESULTS: Human cultured chondrocytes express SERPINE2 in basal condition. This expression increased in response to IL-1α stimulation. In addition, recombinant SERPINE2 induced a clear inhibition of MMP-13 expression in IL-1α-stimulated chondrocytes. This inhibitory effect is likely regulated through a pathway involving ERK 1/2, NF-κB and AP-1. CONCLUSIONS: Taken together, these data demonstrate that SERPINE2 might prevent cartilage catabolism by inhibiting the expression of MMP-13, one of the most relevant collagenases, involved in cartilage breakdown in OA. Public Library of Science 2015-08-25 /pmc/articles/PMC4549255/ /pubmed/26305372 http://dx.doi.org/10.1371/journal.pone.0135979 Text en © 2015 Santoro et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Santoro, Anna
Conde, Javier
Scotece, Morena
Abella, Vanessa
Lois, Ana
Lopez, Veronica
Pino, Jesus
Gomez, Rodolfo
Gomez-Reino, Juan J.
Gualillo, Oreste
SERPINE2 Inhibits IL-1α-Induced MMP-13 Expression in Human Chondrocytes: Involvement of ERK/NF-κB/AP-1 Pathways
title SERPINE2 Inhibits IL-1α-Induced MMP-13 Expression in Human Chondrocytes: Involvement of ERK/NF-κB/AP-1 Pathways
title_full SERPINE2 Inhibits IL-1α-Induced MMP-13 Expression in Human Chondrocytes: Involvement of ERK/NF-κB/AP-1 Pathways
title_fullStr SERPINE2 Inhibits IL-1α-Induced MMP-13 Expression in Human Chondrocytes: Involvement of ERK/NF-κB/AP-1 Pathways
title_full_unstemmed SERPINE2 Inhibits IL-1α-Induced MMP-13 Expression in Human Chondrocytes: Involvement of ERK/NF-κB/AP-1 Pathways
title_short SERPINE2 Inhibits IL-1α-Induced MMP-13 Expression in Human Chondrocytes: Involvement of ERK/NF-κB/AP-1 Pathways
title_sort serpine2 inhibits il-1α-induced mmp-13 expression in human chondrocytes: involvement of erk/nf-κb/ap-1 pathways
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549255/
https://www.ncbi.nlm.nih.gov/pubmed/26305372
http://dx.doi.org/10.1371/journal.pone.0135979
work_keys_str_mv AT santoroanna serpine2inhibitsil1ainducedmmp13expressioninhumanchondrocytesinvolvementoferknfkbap1pathways
AT condejavier serpine2inhibitsil1ainducedmmp13expressioninhumanchondrocytesinvolvementoferknfkbap1pathways
AT scotecemorena serpine2inhibitsil1ainducedmmp13expressioninhumanchondrocytesinvolvementoferknfkbap1pathways
AT abellavanessa serpine2inhibitsil1ainducedmmp13expressioninhumanchondrocytesinvolvementoferknfkbap1pathways
AT loisana serpine2inhibitsil1ainducedmmp13expressioninhumanchondrocytesinvolvementoferknfkbap1pathways
AT lopezveronica serpine2inhibitsil1ainducedmmp13expressioninhumanchondrocytesinvolvementoferknfkbap1pathways
AT pinojesus serpine2inhibitsil1ainducedmmp13expressioninhumanchondrocytesinvolvementoferknfkbap1pathways
AT gomezrodolfo serpine2inhibitsil1ainducedmmp13expressioninhumanchondrocytesinvolvementoferknfkbap1pathways
AT gomezreinojuanj serpine2inhibitsil1ainducedmmp13expressioninhumanchondrocytesinvolvementoferknfkbap1pathways
AT gualillooreste serpine2inhibitsil1ainducedmmp13expressioninhumanchondrocytesinvolvementoferknfkbap1pathways