@article{SadowskaKamedaKrupkovaetal.2018,
  author    = {Sadowska, Aleksandra and Kameda, Takuya and Krupkova, Olga and Wuertz-Kozak, Karin},
  title     = {Osmosensing, osmosignalling and inflammation},
  series = {European cells \& materials},
  volume    = {36},
  journal   = {European cells \& materials},
  publisher = {Ao research institute davos-Ari},
  address   = {Davos},
  issn      = {1473-2262},
  doi       = {10.22203/eCM.v036a17},
  pages     = {231 -- 250},
  year      = {2018},
  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.},
  language  = {en}
}
@misc{KrupkovaSadowskaKamedaetal.2018,
  author    = {Krupkova, Olga and Sadowska, Aleksandra and Kameda, Takuya and Hitzl, Wolfgang and Hausmann, Oliver Nic and Klasen, J{\"u}rgen and Wuertz-Kozak, Karin},
  title     = {p38 MaPK facilitates crosstalk between endoplasmic reticulum stress and IL-6 release in the intervertebral Disc},
  series = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe},
  number    = {705},
  issn      = {1866-8364},
  doi       = {10.25932/publishup-46869},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-468698},
  pages     = {16},
  year      = {2018},
  abstract  = {Degenerative disc disease is associated with increased expression of pro-inflammatory cytokines in the intervertebral disc (IVD). However, it is not completely clear how inflammation arises in the IVD and which cellular compartments are involved in this process. Recently, the endoplasmic reticulum (ER) has emerged as a possible modulator of inflammation in age-related disorders. In addition, ER stress has been associated with the microenvironment of degenerated IVDs. Therefore, the aim of this study was to analyze the effects of ER stress on inflammatory responses in degenerated human IVDs and associated molecular mechanisms. Gene expression of ER stress marker GRP78 and pro-inflammatory cytokines IL-6, IL-8, IL-1 beta, and TNF-alpha was analyzed in human surgical IVD samples (n = 51, Pfirrmann grade 2-5). The expression of GRP78 positively correlated with the degeneration grade in lumbar IVDs and IL-6, but not with IL-1 beta and TNF-alpha. Another set of human surgical IVD samples (n = 25) was used to prepare primary cell cultures. ER stress inducer thapsigargin (Tg, 100 and 500 nM) activated gene and protein expression of IL-6 and induced phosphorylation of p38 MAPK. Both inhibition of p38 MAPK by SB203580 (10 mu M) and knockdown of ER stress effector CCAAT-enhancer-binding protein homologous protein (CHOP) reduced gene and protein expression of IL-6 in Tg-treated cells. Furthermore, the effects of an inflammatory microenvironment on ER stress were tested. TNF-alpha (5 and 10 ng/mL) did not activate ER stress, while IL-1 beta (5 and 10 ng/mL) activated gene and protein expression of GRP78, but did not influence [Ca2+](i) flux and expression of CHOP, indicating that pro-inflammatory cytokines alone may not induce ER stress in vivo. This study showed that IL-6 release in the IVD can be initiated following ER stress and that ER stress mediates IL-6 release through p38 MAPK and CHOP. Therapeutic targeting of ER stress response may reduce the consequences of the harsh microenvironment in degenerated IVD.},
  language  = {en}
}
@misc{SadowskaKamedaKrupkovaetal.2018,
  author    = {Sadowska, Aleksandra and Kameda, Takuya and Krupkova, Olga and W{\"u}rtz-Kozak, Karin},
  title     = {Osmosensing, osmosignalling and inflammation},
  series = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe},
  number    = {693},
  issn      = {1866-8364},
  doi       = {10.25932/publishup-46908},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-469080},
  pages     = {22},
  year      = {2018},
  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 responseelement-binding protein/nuclear factor of activated T-cells 5 (TonEBP/NFAT5), nuclear factor kappa-lightchain-enhancer of activated B cells (NF-kappa B)] in healthy and degenerated IVDs. Finally, an overview of the potential therapeutic targets for modifying osmosensing and osmosignalling in degenerated IVDs is provided.},
  language  = {en}
}