eCM (Eur Cell Mater / e Cells & Materials) Not-for-profit Open Access
Created by Scientists, for Scientists
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2018   Volume No 36 – pages 231-250

Title: Osmosensing, osmosignalling and inflammation: how intervertebral disc cells respond to altered osmolarity

Authors: A Sadowska, T Kameda, O Krupkova, K Wuertz-Kozak

Address: Institute for Biomechanics, D-HEST, ETH Zurich, Hönggerbergring 64, HPP-O12, 8093 Zurich, Switzerland.

E-mail: kwuertz at

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.

Key Words: Intervertebral disc degeneration, degenerative disc disease, osmolarity, hyper-osmolarity, hypo-osmolarity, osmotic, inflammatory, transient receptor potential channel, aquaporin, tonicity-responsive enhancer binding protein.

Publication date: November 19th 2018

Article download: Pages 231-250 (PDF file)

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