UZH-Logo

Maintenance Infos

Inflammatory and catabolic signalling in intervertebral discs: the roles of NF-κB and MAP kinases


Wuertz, Karin; Vo, Nam; Kletsas, Dimitris; Boos, Norbert (2012). Inflammatory and catabolic signalling in intervertebral discs: the roles of NF-κB and MAP kinases. European Cells and Materials, 23:103-119; discussion 119.

Abstract

Painful intervertebral disc disease is characterised not only by an imbalance between anabolic (i.e., matrix synthesis) and catabolic (i.e., matrix degradation) processes, but also by inflammatory mechanisms. The increased expression and synthesis of matrix metalloproteinases and inflammatory factors is mediated by specific signal transduction, in particular the nuclear factor-kappaB (NF-kB) and mitogen-activated protein kinase (MAPK)-mediated pathways. NF-kB and MAPK have been identified as the master regulators of inflammation and catabolism in several musculoskeletal disorders (e.g., osteoarthritis), and recently growing evidence supports the importance of these signalling pathways in painful disc disease. With continuing research exploiting in vitro and in vivo model systems to elucidate the roles of these pathways in disc degeneration, it may be possible in the near future to specifically target these major inflammatory / catabolic signalling pathways to treat painful degenerative disc disease. In this perspective, we aim to summarise the current state of knowledge concerning the inflammatory and catabolic molecular pathways of intervertebral disc disease (IDD), with a detailed description of NF-kB and MAP kinase-mediated signal transduction in disc cells. Furthermore, we will discuss the emerging novel molecular treatment modalities for IDD using pharmacological inhibitors targeting these pathways.

Abstract

Painful intervertebral disc disease is characterised not only by an imbalance between anabolic (i.e., matrix synthesis) and catabolic (i.e., matrix degradation) processes, but also by inflammatory mechanisms. The increased expression and synthesis of matrix metalloproteinases and inflammatory factors is mediated by specific signal transduction, in particular the nuclear factor-kappaB (NF-kB) and mitogen-activated protein kinase (MAPK)-mediated pathways. NF-kB and MAPK have been identified as the master regulators of inflammation and catabolism in several musculoskeletal disorders (e.g., osteoarthritis), and recently growing evidence supports the importance of these signalling pathways in painful disc disease. With continuing research exploiting in vitro and in vivo model systems to elucidate the roles of these pathways in disc degeneration, it may be possible in the near future to specifically target these major inflammatory / catabolic signalling pathways to treat painful degenerative disc disease. In this perspective, we aim to summarise the current state of knowledge concerning the inflammatory and catabolic molecular pathways of intervertebral disc disease (IDD), with a detailed description of NF-kB and MAP kinase-mediated signal transduction in disc cells. Furthermore, we will discuss the emerging novel molecular treatment modalities for IDD using pharmacological inhibitors targeting these pathways.

Citations

53 citations in Web of Science®
54 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

171 downloads since deposited on 30 Apr 2012
55 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2012
Deposited On:30 Apr 2012 13:00
Last Modified:05 Apr 2016 15:47
Publisher:European Cells and Materials
ISSN:1473-2262
PubMed ID:22354461

Download

[img]
Preview
Content: Published Version
Filetype: PDF
Size: 1MB

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations