@article{KrupkovaZvickWuertzKozak2017,
  author    = {Krupkova, Olga and Zvick, Johannes and W{\"u}rtz-Kozak, Karin},
  title     = {The role of transient receptor potential channels in joint diseases},
  series = {European cells \& materials},
  volume    = {34},
  journal   = {European cells \& materials},
  publisher = {Univ. of Wales},
  address   = {Aberystwyth},
  issn      = {1473-2262},
  doi       = {10.22203/eCM.v034a12},
  pages     = {180 -- 201},
  year      = {2017},
  abstract  = {Transient receptor potential channels (TRP channels) are cation selective transmembrane receptors with diverse structures, activation mechanisms and physiological functions. TRP channels act as cellular sensors for a plethora of stimuli, including temperature, membrane voltage, oxidative stress, mechanical stimuli, pH and endogenous as well as exogenous ligands, thereby illustrating their versatility. As such, TRP channels regulate various functions in both excitable and non-excitable cells, mainly by mediating Ca2+ homeostasis. Dysregulation of TRP channels is implicated in many pathologies, including cardiovascular diseases, muscular dystrophies and hyperalgesia. However, the importance of TRP channel expression, physiological function and regulation in chondrocytes and intervertebral disc (IVD) cells is largely unexplored. Osteoarthritis (OA) and degenerative disc disease (DDD) are chronic age-related disorders that significantly affect the quality of life by causing pain, activity limitation and disability. Furthermore, currently available therapies cannot effectively slow-down or stop progression of these diseases. Both OA and DDD are characterised by reduced tissue cellularity, enhanced inflammatory responses and molecular, structural and mechanical alterations of the extracellular matrix, hence affecting load distribution and reducing joint flexibility. However, knowledge on how chondrocytes and IVD cells sense their microenvironment and respond to its changes is still limited. In this review, we introduced six families of mammalian TRP channels, their mechanisms of activation as well as activation-driven cellular consequences. We summarised the current knowledge on TRP channel expression and activity in chondrocytes and IVD cells and the significance of TRP channels as therapeutic targets for the treatment of OA and DDD.},
  language  = {en}
}
@misc{KrupkovaSmoldersWuertzKozaketal.2018,
  author    = {Krupkova, Olga and Smolders, Lucas and W{\"u}rtz-Kozak, Karin and Cook, James and Pozzi, Antonio},
  title     = {The pathobiology of the meniscus},
  series = {Frontiers in veterinary science},
  volume    = {5},
  journal   = {Frontiers in veterinary science},
  publisher = {Frontiers Research Foundation},
  address   = {Lausanne},
  issn      = {2297-1769},
  doi       = {10.3389/fvets.2018.00073},
  pages     = {15},
  year      = {2018},
  abstract  = {Serious knee pain and related disability have an annual prevalence of approximately 25\% on those over the age of 55 years. As curative treatments for the common knee problems are not available to date, knee pathologies typically progress and often lead to osteoarthritis (OA). While the roles that the meniscus plays in knee biomechanics are well characterized, biological mechanisms underlying meniscus pathophysiology and roles in knee pain and OA progression are not fully clear. Experimental treatments for knee disorders that are successful in animal models often produce unsatisfactory results in humans due to species differences or the inability to fully replicate disease progression in experimental animals. The use of animals with spontaneous knee pathologies, such as dogs, can significantly help addressing this issue. As microscopic and macroscopic anatomy of the canine and human menisci are similar, spontaneous meniscal pathologies in canine patients are thought to be highly relevant for translational medicine. However, it is not clear whether the biomolecular mechanisms of pain, degradation of extracellular matrix, and inflammatory responses are species dependent. The aims of this review are (1) to provide an overview of the anatomy, physiology, and pathology of the human and canine meniscus, (2) to compare the known signaling pathways involved in spontaneous meniscus pathology between both species, and (3) to assess the relevance of dogs with spontaneous meniscal pathology as a translational model. Understanding these mechanisms in human and canine meniscus can help to advance diagnostic and therapeutic strategies for painful knee disorders and improve clinical decision making.},
  language  = {en}
}
@article{MouserArkesteijnvanDijketal.2019,
  author    = {Mouser, Vivian H. M. and Arkesteijn, Irene T. M. and van Dijk, Bart G. M. and W{\"u}rtz-Kozak, Karin and Ito, Keita},
  title     = {Hypotonicity differentially affects inflammatory marker production by nucleus pulposus tissue in simulated disc degeneration versus herniation},
  series = {Journal of orthopaedic research},
  volume    = {37},
  journal   = {Journal of orthopaedic research},
  number    = {5},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {0736-0266},
  doi       = {10.1002/jor.24268},
  pages     = {1110 -- 1116},
  year      = {2019},
  abstract  = {Inflammatory cytokines play an important role in intervertebral disc degeneration. Although largely produced by immune cells, nucleus pulposus (NP) cells can also secrete them under various conditions, for example, under free swelling. Thus, tissue hypotonicity may be an inflammatory trigger for NP cells. The aim of this study was to investigate whether decreased tonicity under restricted swelling conditions (as occurring in early disc degeneration) could initiate an inflammatory cascade that mediates further degeneration. Healthy bovine NP tissue was balanced against different PEG concentrations (0-30\%) to obtain various tissue tonicities. Samples were then placed in an artificial annulus (fixed volume) and were cultured for 3, 7, or 21 days, with free swelling NP as control. Tissue content (water, glycosaminoglycan, collagen) was analyzed, and both the tissue and medium were screened for tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), prostaglandin-E-2 (PGE(2)), and nitric oxide (NO). A range of tonicities (isotonic to hypotonic) was present at day 3 in the PEG-treated samples. However, during culture, the tonicity range narrowed as GAGs leached from the tissue. TNF-alpha and IL-1 beta were below detection limits in all conditions, while mid- and downstream inflammatory cytokines were detected. This may suggest that the extracellular environment directly affects NP cells instead of inducing a classical inflammatory cascade. Furthermore, IL-8 increased in swelling restricted samples, while IL-6 and PGE(2) were elevated in free swelling controls. These findings may suggest the involvement of different mechanisms in disc degeneration with intact AF compared to herniation, and encourage further investigation. (c) 2019 The Authors. Journal of Orthopaedic Research (R) Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res},
  language  = {en}
}
@article{LoepfeDussZafeiropoulouetal.2019,
  author    = {L{\"o}pfe, Moira and Duss, Anja and Zafeiropoulou, Katerina-Alexandra and Bjoergvinsdottir, Oddny and Eglin, David and Fortunato, Giuseppino and Klasen, J{\"u}rgen and Ferguson, Stephen J. and W{\"u}rtz-Kozak, Karin and Krupkova, Olga},
  title     = {Electrospray-Based Microencapsulation of Epigallocatechin 3-Gallate for Local Delivery into the Intervertebral Disc},
  series = {Pharmaceutics},
  volume    = {11},
  journal   = {Pharmaceutics},
  number    = {9},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {1999-4923},
  doi       = {10.3390/pharmaceutics11090435},
  pages     = {15},
  year      = {2019},
  abstract  = {Locally delivered anti-inflammatory compounds can restore the homeostasis of the degenerated intervertebral disc (IVD). With beneficial effects on IVD cells, epigallocatechin 3-gallate (EGCG) is a promising therapeutic candidate. However, EGCG is prone to rapid degradation and/or depletion. Therefore, the purpose of this study was to develop a method for controlled EGCG delivery in the degenerated IVD. Primary IVD cells were isolated from human donors undergoing IVD surgeries. EGCG was encapsulated into microparticles by electrospraying of glutaraldehyde-crosslinked gelatin. The resulting particles were characterized in terms of cytocompatibility and anti-inflammatory activity, and combined with a thermoresponsive carrier to produce an injectable EGCG delivery system. Subsequently, electrospraying was scaled up using the industrial NANOSPIDER (TM) technology. The produced EGCG microparticles reduced the expression of inflammatory (IL-6, IL-8, COX-2) and catabolic (MMP1, MMP3, MMP13) mediators in pro-inflammatory 3D cell cultures. Combining the EGCG microparticles with the carrier showed a trend towards modulating EGCG activity/release. Electrospray upscaling was achieved, leading to particles with homogenous spherical morphologies. In conclusion, electrospray-based encapsulation of EGCG resulted in cytocompatible microparticles that preserved the activity of EGCG and showed the potential to control EGCG release, thus favoring IVD health by downregulating local inflammation. Future studies will focus on further exploring the biological activity of the developed delivery system for potential clinical use.},
  language  = {en}
}