title: Inflammatory and catabolic signalling in intervertebral discs: the roles of NF-κB and MAP kinases.
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.
authors.affiliation: Spine Research Group, Competence Centre for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland. karin.wuertz@cabmm.uzh.ch
authors.forename: Karin
authors.initials: K
authors.lastname: Wuertz
authors.forename: Nam
authors.initials: N
authors.lastname: Vo
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kletsas
authors.forename: Norbert
authors.initials: N
authors.lastname: Boos
mesh_terms: D015299:Discitis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007403:Intervertebral Disc / Q000378:metabolism*; D055959:Intervertebral Disc Degeneration / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D020782:Matrix Metalloproteinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018836:Inflammation Mediators; D016328:NF-kappa B; D020928:Mitogen-Activated Protein Kinases; D020782:Matrix Metalloproteinases