RT Journal Article
T1 SERPINE2 Inhibits IL-1α-Induced MMP-13 Expression in Human Chondrocytes: Involvement of ERK/NF-κB/AP-1 Pathways
A1 Santoro, Anna
A1 Conde, Javier
A1 Scotece, Morena
A1 Abella, Vanessa
A1 Lois, Ana
A1 López, Verónica
A1 Pino, Jesús
A1 Gómez, Rodolfo
A1 Gómez-Reino Carnota, Juan Jesús
A1 Gualillo, Oreste
AB ObjectivesOsteoarthritis (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.MethodsSERPINE2 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.ResultsHuman 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.ConclusionsTaken 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.
PB PLOS
YR 2015
FD 2015
LK http://hdl.handle.net/10347/22107
UL http://hdl.handle.net/10347/22107
LA eng
NO Santoro A, Conde J, Scotece M, Abella V, Lois A, Lopez V, et al. (2015) SERPINE2 Inhibits IL-1α-Induced MMP-13 Expression in Human Chondrocytes: Involvement of ERK/NF-κB/AP-1 Pathways. PLoS ONE 10(8): e0135979. https://doi.org/10.1371/journal.pone.0135979
NO Oreste Gualillo is Staff Personnel of Xunta de Galicia (SERGAS) through a research-staff stabilization contract (ISCIII/SERGAS). OG is a member of RETICS Programme, RD12/0009/0008 (RIER: Red de Investigación en Inflamación y Enfermedades Reumáticas) via Instituto de Salud Carlos III (ISCIII). The OG work was funded by Instituto de Salud Carlos III and FEDER (European Fund of Regional Development) (grants PI14/00016 and PIE13/00024). Vanessa Abella is a recipient of a predoctoral fellowship from ESF (European Social Fund) grant from Xunta de Galicia through a contract signed with University of Coruña. Morena Scotece is a recipient of the “FPU” Program of the Spanish Ministry of Education. Javier Conde is a recipient of a fellowship from the Foundation IDIS-Ramón Dominguez. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
DS Minerva
RD 24 abr 2026