Cargando…

Pathophysiology of osteoarthritis: canonical NF-κB/IKKβ-dependent and kinase-independent effects of IKKα in cartilage degradation and chondrocyte differentiation

Osteoarthritis (OA), a whole-joint disease driven by abnormal biomechanics and attendant cell-derived and tissue-derived factors, is a rheumatic disease with the highest prevalence, representing a severe health burden with a tremendous economic impact. Members of the nuclear factor κB (NF-κB) family...

Descripción completa

Detalles Bibliográficos
Autores principales: Olivotto, Eleonora, Otero, Miguel, Marcu, Kenneth B, Goldring, Mary B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632142/
https://www.ncbi.nlm.nih.gov/pubmed/26557379
http://dx.doi.org/10.1136/rmdopen-2015-000061
_version_ 1782398969004949504
author Olivotto, Eleonora
Otero, Miguel
Marcu, Kenneth B
Goldring, Mary B
author_facet Olivotto, Eleonora
Otero, Miguel
Marcu, Kenneth B
Goldring, Mary B
author_sort Olivotto, Eleonora
collection PubMed
description Osteoarthritis (OA), a whole-joint disease driven by abnormal biomechanics and attendant cell-derived and tissue-derived factors, is a rheumatic disease with the highest prevalence, representing a severe health burden with a tremendous economic impact. Members of the nuclear factor κB (NF-κB) family orchestrate mechanical, inflammatory and oxidative stress-activated processes, thus representing a potential therapeutic target in OA disease. The two pivotal kinases, IκB kinase (IKK) α and IKKβ, activate NF-κB dimers that might translocate to the nucleus and regulate the expression of specific target genes involved in extracellular matrix remodelling and terminal differentiation of chondrocytes. IKKα, required for the activation of the so-called non-canonical pathway, has a number of NF-κB-independent and kinase-independent functions in vivo and in vitro, including controlling chondrocyte hypertrophic differentiation and collagenase activity. In this short review, we will discuss the role of NF-κB signalling in OA pathology, with emphasis on the functional effects of IKKα that are independent of its kinase activity and NF-κB activation.
format Online
Article
Text
id pubmed-4632142
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher BMJ Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-46321422015-11-09 Pathophysiology of osteoarthritis: canonical NF-κB/IKKβ-dependent and kinase-independent effects of IKKα in cartilage degradation and chondrocyte differentiation Olivotto, Eleonora Otero, Miguel Marcu, Kenneth B Goldring, Mary B RMD Open Proceedings from OsteoRheumatology 2014 Osteoarthritis (OA), a whole-joint disease driven by abnormal biomechanics and attendant cell-derived and tissue-derived factors, is a rheumatic disease with the highest prevalence, representing a severe health burden with a tremendous economic impact. Members of the nuclear factor κB (NF-κB) family orchestrate mechanical, inflammatory and oxidative stress-activated processes, thus representing a potential therapeutic target in OA disease. The two pivotal kinases, IκB kinase (IKK) α and IKKβ, activate NF-κB dimers that might translocate to the nucleus and regulate the expression of specific target genes involved in extracellular matrix remodelling and terminal differentiation of chondrocytes. IKKα, required for the activation of the so-called non-canonical pathway, has a number of NF-κB-independent and kinase-independent functions in vivo and in vitro, including controlling chondrocyte hypertrophic differentiation and collagenase activity. In this short review, we will discuss the role of NF-κB signalling in OA pathology, with emphasis on the functional effects of IKKα that are independent of its kinase activity and NF-κB activation. BMJ Publishing Group 2015-08-15 /pmc/articles/PMC4632142/ /pubmed/26557379 http://dx.doi.org/10.1136/rmdopen-2015-000061 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
spellingShingle Proceedings from OsteoRheumatology 2014
Olivotto, Eleonora
Otero, Miguel
Marcu, Kenneth B
Goldring, Mary B
Pathophysiology of osteoarthritis: canonical NF-κB/IKKβ-dependent and kinase-independent effects of IKKα in cartilage degradation and chondrocyte differentiation
title Pathophysiology of osteoarthritis: canonical NF-κB/IKKβ-dependent and kinase-independent effects of IKKα in cartilage degradation and chondrocyte differentiation
title_full Pathophysiology of osteoarthritis: canonical NF-κB/IKKβ-dependent and kinase-independent effects of IKKα in cartilage degradation and chondrocyte differentiation
title_fullStr Pathophysiology of osteoarthritis: canonical NF-κB/IKKβ-dependent and kinase-independent effects of IKKα in cartilage degradation and chondrocyte differentiation
title_full_unstemmed Pathophysiology of osteoarthritis: canonical NF-κB/IKKβ-dependent and kinase-independent effects of IKKα in cartilage degradation and chondrocyte differentiation
title_short Pathophysiology of osteoarthritis: canonical NF-κB/IKKβ-dependent and kinase-independent effects of IKKα in cartilage degradation and chondrocyte differentiation
title_sort pathophysiology of osteoarthritis: canonical nf-κb/ikkβ-dependent and kinase-independent effects of ikkα in cartilage degradation and chondrocyte differentiation
topic Proceedings from OsteoRheumatology 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632142/
https://www.ncbi.nlm.nih.gov/pubmed/26557379
http://dx.doi.org/10.1136/rmdopen-2015-000061
work_keys_str_mv AT olivottoeleonora pathophysiologyofosteoarthritiscanonicalnfkbikkbdependentandkinaseindependenteffectsofikkaincartilagedegradationandchondrocytedifferentiation
AT oteromiguel pathophysiologyofosteoarthritiscanonicalnfkbikkbdependentandkinaseindependenteffectsofikkaincartilagedegradationandchondrocytedifferentiation
AT marcukennethb pathophysiologyofosteoarthritiscanonicalnfkbikkbdependentandkinaseindependenteffectsofikkaincartilagedegradationandchondrocytedifferentiation
AT goldringmaryb pathophysiologyofosteoarthritiscanonicalnfkbikkbdependentandkinaseindependenteffectsofikkaincartilagedegradationandchondrocytedifferentiation