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...
Autores principales: | , , , |
---|---|
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 |