Osmosensing, osmosignalling and inflammation: how intervertebral disc cells respond to altered osmolarity
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Author / Producer
Date
2018
Publication Type
Review Article
ETH Bibliography
yes
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Abstract
Intervertebral disc (IVD) cells are naturally exposed to high osmolarity and complex mechanical loading, which drive microenvironmental osmotic changes. Age- and degeneration-induced degradation of the IVD’s extracellular matrix causes osmotic imbalance, which, together with an altered function of cellular receptors and signalling pathways, instigates local osmotic stress. Cellular responses to osmotic stress include osmoadaptation and activation of pro-inflammatory pathways. This review summarises the current knowledge on how IVD cells sense local osmotic changes and translate these signals into physiological or pathophysiological responses, with a focus on inflammation. Furthermore, it discusses the expression and function of putative membrane osmosensors (e.g. solute carrier transporters, transient receptor potential channels, aquaporins and acid-sensing ion channels) and osmosignalling mediators [e.g. tonicity response-element-binding protein/nuclear factor of activated T-cells 5 (TonEBP/NFAT5), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)] in healthy and degenerated IVDs. Finally, an overview of the potential therapeutic targets for modifying osmosensing and osmosignalling in degenerated IVDs is provided.
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Publication status
published
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Editor
Book title
Journal / series
Volume
36
Pages / Article No.
231 - 250
Publisher
AO Research Institute Davos
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
IVD; degenerative disc disease; Intervertebral disc degeneration; osmolarity; Transient receptor potential channels (TRP); tonicity-responsive enhancer binding protein; aquaporin; inflammatory
Organisational unit
09597 - Würtz, Karin (SNF-Professur) (ehemalig) / Würtz, Karin (SNF-Professur) (former)