Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast-derived ADAMTS-7 and -12.

Failure of therapeutic approaches for the treatment of osteoarthritis (OA) based on the inhibition of metalloproteinases, might be because of their constitutive expression in homeostasis, together with their network complexity. The knowledge of this network would contribute to selective target patho...

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Autores: Perez-Garcia, Selene, Carrion, Mar, Villanueva-Romero, Raul, Hermida Gómez, Tamara, Fernandez Moreno, Mercedes, Mellado, Mario, BLANCO GARCIA, FRANCISCO JAVIER, Juarranz, Yasmina, Gomariz, Rosa P
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/15942
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533528/pdf/JCMM-23-3974.pdf
https://www.ncbi.nlm.nih.gov/pubmed/30903650
http://hdl.handle.net/20.500.11940/15942
Access Level:acceso abierto
Palabra clave:Wnt Signaling Pathway
Humans
Fibroblasts
Cartilage Oligomeric Matrix Protein
Interleukin-1beta
Extracellular Matrix
Core Binding Factor Alpha 1 Subunit
Synovial Membrane
Osteoarthritis
Fibronectins
Aged
Cartilage
anciano
membrana sinovial
fibronectinas
fibroblastos
cartílago
matriz extracelular
subunidad alfa 1 del factor de unión central
proteína oligomérica de la matriz del cartílago
interleucina-1beta
humanos
osteoartritis
vía de señalización Wnt
CHUAC
INIBIC
id ES_7fb2494fc16ef3f63a3a6f1cc068f9ee
oai_identifier_str oai:runa.sergas.gal:20.500.11940/15942
network_acronym_str ES
network_name_str España
repository_id_str
spelling Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast-derived ADAMTS-7 and -12.Perez-Garcia, SeleneCarrion, MarVillanueva-Romero, RaulHermida Gómez, TamaraFernandez Moreno, MercedesMellado, MarioBLANCO GARCIA, FRANCISCO JAVIERJuarranz, YasminaGomariz, Rosa PWnt Signaling PathwayHumansFibroblastsCartilage Oligomeric Matrix ProteinInterleukin-1betaExtracellular MatrixCore Binding Factor Alpha 1 SubunitSynovial MembraneOsteoarthritisFibronectinsAgedCartilageancianomembrana sinovialfibronectinasfibroblastoscartílagomatriz extracelularsubunidad alfa 1 del factor de unión centralproteína oligomérica de la matriz del cartílagointerleucina-1betahumanososteoartritisvía de señalización WntCHUACINIBICFailure of therapeutic approaches for the treatment of osteoarthritis (OA) based on the inhibition of metalloproteinases, might be because of their constitutive expression in homeostasis, together with their network complexity. The knowledge of this network would contribute to selective target pathological conditions. In this sense, blockade of mediators produced by neighbouring joint cells, such as synovial fibroblasts (SF), would prevent cartilage damage. Thus, we studied the contribution of ADAMTS-7 and -12 from SF to cartilage oligomeric matrix protein (COMP) degradation, and the signalling pathways involved in their expression. We report for the first time in SF, the involvement of ERK-Runx2 axis and Wnt/beta-catenin signalling in ADAMTS-12 and ADAMTS-7 expressions, respectively, with the subsequent consequences in COMP degradation from cartilage extracellular matrix. After stimulation with IL-1beta or fibronectin fragments, we showed that ERK inhibition decreased Runx2 activation and ADAMTS-12 expression in OA-SF, also reducing Fn-fs-induced COMP degradation. Blockage of Wnt signalling by DKK1 reduced ADAMTS-7 and COMP degradation in OA-SF as well. In addition, Wnt7B expression was induced by IL-1beta and by itself, also increasing ADAMTS-7. Our results could contribute to the development of disease-modifying OA drugs targeting ADAMTS-7 and -12 for the prevention of extracellular matrix components degradation like COMP.2019info:eu-repo/semantics/articlehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533528/pdf/JCMM-23-3974.pdfhttps://www.ncbi.nlm.nih.gov/pubmed/30903650http://hdl.handle.net/20.500.11940/15942reponame:RUNA. Repositorio da Consellería de Sanidade e Sergasinstname:Servizo Galego de Saúde (SERGAS)Ingléshttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:runa.sergas.gal:20.500.11940/159422026-06-12T08:40:47Z
dc.title.none.fl_str_mv Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast-derived ADAMTS-7 and -12.
title Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast-derived ADAMTS-7 and -12.
spellingShingle Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast-derived ADAMTS-7 and -12.
Perez-Garcia, Selene
Wnt Signaling Pathway
Humans
Fibroblasts
Cartilage Oligomeric Matrix Protein
Interleukin-1beta
Extracellular Matrix
Core Binding Factor Alpha 1 Subunit
Synovial Membrane
Osteoarthritis
Fibronectins
Aged
Cartilage
anciano
membrana sinovial
fibronectinas
fibroblastos
cartílago
matriz extracelular
subunidad alfa 1 del factor de unión central
proteína oligomérica de la matriz del cartílago
interleucina-1beta
humanos
osteoartritis
vía de señalización Wnt
CHUAC
INIBIC
title_short Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast-derived ADAMTS-7 and -12.
title_full Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast-derived ADAMTS-7 and -12.
title_fullStr Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast-derived ADAMTS-7 and -12.
title_full_unstemmed Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast-derived ADAMTS-7 and -12.
title_sort Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast-derived ADAMTS-7 and -12.
dc.creator.none.fl_str_mv Perez-Garcia, Selene
Carrion, Mar
Villanueva-Romero, Raul
Hermida Gómez, Tamara
Fernandez Moreno, Mercedes
Mellado, Mario
BLANCO GARCIA, FRANCISCO JAVIER
Juarranz, Yasmina
Gomariz, Rosa P
author Perez-Garcia, Selene
author_facet Perez-Garcia, Selene
Carrion, Mar
Villanueva-Romero, Raul
Hermida Gómez, Tamara
Fernandez Moreno, Mercedes
Mellado, Mario
BLANCO GARCIA, FRANCISCO JAVIER
Juarranz, Yasmina
Gomariz, Rosa P
author_role author
author2 Carrion, Mar
Villanueva-Romero, Raul
Hermida Gómez, Tamara
Fernandez Moreno, Mercedes
Mellado, Mario
BLANCO GARCIA, FRANCISCO JAVIER
Juarranz, Yasmina
Gomariz, Rosa P
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Wnt Signaling Pathway
Humans
Fibroblasts
Cartilage Oligomeric Matrix Protein
Interleukin-1beta
Extracellular Matrix
Core Binding Factor Alpha 1 Subunit
Synovial Membrane
Osteoarthritis
Fibronectins
Aged
Cartilage
anciano
membrana sinovial
fibronectinas
fibroblastos
cartílago
matriz extracelular
subunidad alfa 1 del factor de unión central
proteína oligomérica de la matriz del cartílago
interleucina-1beta
humanos
osteoartritis
vía de señalización Wnt
CHUAC
INIBIC
topic Wnt Signaling Pathway
Humans
Fibroblasts
Cartilage Oligomeric Matrix Protein
Interleukin-1beta
Extracellular Matrix
Core Binding Factor Alpha 1 Subunit
Synovial Membrane
Osteoarthritis
Fibronectins
Aged
Cartilage
anciano
membrana sinovial
fibronectinas
fibroblastos
cartílago
matriz extracelular
subunidad alfa 1 del factor de unión central
proteína oligomérica de la matriz del cartílago
interleucina-1beta
humanos
osteoartritis
vía de señalización Wnt
CHUAC
INIBIC
description Failure of therapeutic approaches for the treatment of osteoarthritis (OA) based on the inhibition of metalloproteinases, might be because of their constitutive expression in homeostasis, together with their network complexity. The knowledge of this network would contribute to selective target pathological conditions. In this sense, blockade of mediators produced by neighbouring joint cells, such as synovial fibroblasts (SF), would prevent cartilage damage. Thus, we studied the contribution of ADAMTS-7 and -12 from SF to cartilage oligomeric matrix protein (COMP) degradation, and the signalling pathways involved in their expression. We report for the first time in SF, the involvement of ERK-Runx2 axis and Wnt/beta-catenin signalling in ADAMTS-12 and ADAMTS-7 expressions, respectively, with the subsequent consequences in COMP degradation from cartilage extracellular matrix. After stimulation with IL-1beta or fibronectin fragments, we showed that ERK inhibition decreased Runx2 activation and ADAMTS-12 expression in OA-SF, also reducing Fn-fs-induced COMP degradation. Blockage of Wnt signalling by DKK1 reduced ADAMTS-7 and COMP degradation in OA-SF as well. In addition, Wnt7B expression was induced by IL-1beta and by itself, also increasing ADAMTS-7. Our results could contribute to the development of disease-modifying OA drugs targeting ADAMTS-7 and -12 for the prevention of extracellular matrix components degradation like COMP.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533528/pdf/JCMM-23-3974.pdf
https://www.ncbi.nlm.nih.gov/pubmed/30903650
http://hdl.handle.net/20.500.11940/15942
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533528/pdf/JCMM-23-3974.pdf
https://www.ncbi.nlm.nih.gov/pubmed/30903650
http://hdl.handle.net/20.500.11940/15942
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:RUNA. Repositorio da Consellería de Sanidade e Sergas
instname:Servizo Galego de Saúde (SERGAS)
instname_str Servizo Galego de Saúde (SERGAS)
reponame_str RUNA. Repositorio da Consellería de Sanidade e Sergas
collection RUNA. Repositorio da Consellería de Sanidade e Sergas
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301629

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