TY  - JOUR
A1  - Kang, Mi-Sun
A1  - Lim, Hae-Soon
A1  - Oh, Jong-Suk
A1  - Lim, You-jin
A1  - Wuertz-Kozak, Karin
A1  - Harro, Janette M.
A1  - Shirtliff, Mark E.
A1  - Achermann, Yvonne
T1  - Antimicrobial activity of Lactobacillus salivarius and Lactobacillus fermentum against Staphylococcus aureus
JF  - Pathogens and disease / Federation of European Microbiology Societies
N2  - The increasing prevalence of methicillin-resistant Staphylococcus aureus has become a major public health threat. While lactobacilli were recently found useful in combating various pathogens, limited data exist on their therapeutic potential for S. aureus infections. The aim of this study was to determine whether Lactobacillus salivarius was able to produce bactericidal activities against S. aureus and to determine whether the inhibition was due to a generalized reduction in pH or due to secreted Lactobacillus product(s). We found an 8.6-log10 reduction of planktonic and a 6.3-log10 reduction of biofilm S. aureus. In contrast, the previously described anti-staphylococcal effects of L. fermentum only caused a 4.0-log10 reduction in planktonic S. aureus cells, with no effect on biofilm S. aureus cells. Killing of S. aureus was partially pH dependent, but independent of nutrient depletion. Cell-free supernatant that was pH neutralized and heat inactivated or proteinase K treated had significantly reduced killing of L. salivarius than with pH-neutralized supernatant alone. Proteomic analysis of the L. salivarius secretome identified a total of five secreted proteins including a LysM-containing peptidoglycan binding protein and a protein peptidase M23B. These proteins may represent potential novel anti-staphylococcal agents that could be effective against S. aureus biofilms.
KW  - antibacterial activity
KW  - biofilm
KW  - Lactobacillus fermentum
KW  - Lactobacillus salivarius
KW  - LysM
KW  - Staphylococcus aureus
Y1  - 2017
U6  - https://doi.org/10.1093/femspd/ftx009
SN  - 2049-632X
VL  - 75
IS  - 2
PB  - Oxford Univ. Press
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Sadowska, Aleksandra
A1  - Kameda, Takuya
A1  - Krupkova, Olga
A1  - Wuertz-Kozak, Karin
T1  - Osmosensing, osmosignalling and inflammation
BT  - how intervertebral disc cells respond to altered osmolarity
JF  - European cells & materials
N2  - 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.
KW  - Intervertebral disc degeneration
KW  - degenerative disc disease
KW  - osmolarity
KW  - hyper-osmolarity
KW  - hypo-osmolarity
KW  - osmotic
KW  - inflammatory
KW  - transient receptor potential channel
KW  - aquaporin
KW  - tonicity-responsive enhancer binding protein
Y1  - 2018
U6  - https://doi.org/10.22203/eCM.v036a17
SN  - 1473-2262
VL  - 36
SP  - 231
EP  - 250
PB  - Ao research institute davos-Ari
CY  - Davos
ER  - 
TY  - GEN
A1  - He, Yangyang
A1  - Wuertz-Kozak, Karin
A1  - Kuehl, Linn K.
A1  - Wippert, Pia-Maria
T1  - Extracellular vesicles: potential mediators of psychosocial stress contribution to osteoporosis?
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Osteoporosis is characterized by low bone mass and damage to the bone tissue’s microarchitecture, leading to increased fracture risk. Several studies have provided evidence for associations between psychosocial stress and osteoporosis through various pathways, including the hypothalamic-pituitary-adrenocortical axis, the sympathetic nervous system, and other endocrine factors. As psychosocial stress provokes oxidative cellular stress with consequences for mitochondrial function and cell signaling (e.g., gene expression, inflammation), it is of interest whether extracellular vesicles (EVs) may be a relevant biomarker in this context or act by transporting substances. EVs are intercellular communicators, transfer substances encapsulated in them, modify the phenotype and function of target cells, mediate cell-cell communication, and, therefore, have critical applications in disease progression and clinical diagnosis and therapy. This review summarizes the characteristics of EVs, their role in stress and osteoporosis, and their benefit as biological markers. We demonstrate that EVs are potential mediators of psychosocial stress and osteoporosis and may be beneficial in innovative research settings.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1166 
KW  - allostatic load
KW  - bone remodeling
KW  - microRNA
KW  - osteoblast
KW  - osteoclast
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-523007
SN  - 1866-8372
IS  - 11
ER  - 
TY  - JOUR
A1  - Krupkova, Olga
A1  - Sadowska, Aleksandra
A1  - Kameda, Takuya
A1  - Hitzl, Wolfgang
A1  - Hausmann, Oliver Nic
A1  - Klasen, Jürgen
A1  - Wuertz-Kozak, Karin
T1  - p38 MaPK Facilitates crosstalk Between endoplasmic reticulum stress and IL-6 release in the intervertebral Disc
JF  - Frontiers in Immunology
N2  - 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.
KW  - intervertebral disc
KW  - inflammation
KW  - endoplasmic reticulum stress
KW  - p38 MAPK
KW  - CHOP
KW  - GADD153
KW  - GRP78
KW  - IL-6
Y1  - 2018
U6  - https://doi.org/10.3389/fimmu.2018.01706
SN  - 1664-3224
VL  - 9
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Randall, Matthew J.
A1  - Jüngel, Astrid
A1  - Rimann, Markus
A1  - Wuertz-Kozak, Karin
T1  - Advances in the biofabrication of 3D Skin in vitro
BT  - healthy and pathological models
JF  - Frontiers in Bioengineeringand Biotechnology
N2  - The relevance for in vitro three-dimensional (3D) tissue culture of skin has been present for almost a century. From using skin biopsies in organ culture, to vascularized organotypic full-thickness reconstructed human skin equivalents, in vitro tissue regeneration of 3D skin has reached a golden era. However, the reconstruction of 3D skin still has room to grow and develop. The need for reproducible methodology, physiological structures and tissue architecture, and perfusable vasculature are only recently becoming a reality, though the addition of more complex structures such as glands and tactile corpuscles require advanced technologies. In this review, we will discuss the current methodology for biofabrication of 3D skin models and highlight the advantages and disadvantages of the existing systems as well as emphasize how new techniques can aid in the production of a truly physiologically relevant skin construct for preclinical innovation.
Y1  - 2018
U6  - https://doi.org/10.3389/fbioe.2018.00154
SN  - 2296-4185
VL  - 6
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Wuertz-Kozak, Karin
A1  - Bleisch, Dominique
A1  - Nadi, Najia
A1  - Proemmel, Peter
A1  - Hitzl, Wolfgang
A1  - Kessler, Thomas M. M.
A1  - Gautschi, Oliver P.
A1  - Hausmann, Oliver N.
T1  - Sexual and urinary function following anterior lumbar surgery in females
JF  - Neurourology and urodynamics
N2  - Aims Anterior lumbar interbody fusion procedures (ALIF) and total disc replacement (TDR) with anterior exposure of the lumbar spine entail a risk of a vascular injury and dysfunction of the sympathetic and parasympathetic nerves due to disturbance of the inferior and superior hypogastric plexus. While retrograde ejaculation is a known complication of the anterior spinal approach in males, post-operative sexual as well as urinary function in females has not yet been thoroughly investigated and was hence the aim of this study. Methods Fifteen female patients documented their sexual and urinary function preoperatively, 3 months and 6 months postoperatively, using the validated questionnaires FSFI (Female Sexual Function Index) and ICIQ (International Consultation of Incontinence Questionnaire). Randomization tests were used to statistically analyze expectation values over time (two-sided, P < 0.05). Results While no statistically significant change in the total FSFI score occurred over time, a significant increase in FSFI desire score was noted between preoperative (2.95 +/- 0.8) and 6 months follow-up (3.51 +/- 0.6, P = 0.02). Urinary continence remained unchanged over time. Conclusion In summary, ALIF and lumbar TDR do not seem to negatively influence sexual and urinary function in females. In contrast, increased sexual desire was noted, likely secondary to post-surgical pain relief.
KW  - ALIF
KW  - dysfunction
KW  - FSFI
KW  - ICIQ
KW  - questionnaire
KW  - TDR
KW  - women
Y1  - 2018
U6  - https://doi.org/10.1002/nau.23874
SN  - 0733-2467
SN  - 1520-6777
VL  - 38
IS  - 2
SP  - 632
EP  - 636
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - GEN
A1  - Krupkova, Olga
A1  - Sadowska, Aleksandra
A1  - Kameda, Takuya
A1  - Hitzl, Wolfgang
A1  - Hausmann, Oliver Nic
A1  - Klasen, Jürgen
A1  - Wuertz-Kozak, Karin
T1  - p38 MaPK facilitates crosstalk between endoplasmic reticulum stress and IL-6 release in the intervertebral Disc
T2  - Postprints der Universität Potsdam : Humanwissenschaftliche Reihe
N2  - 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.
T3  - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 705 
KW  - intervertebral disc
KW  - inflammation
KW  - endoplasmic reticulum stress
KW  - p38 MAPK
KW  - CHOP
KW  - GADD153
KW  - GRP78
KW  - IL-6
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-468698
SN  - 1866-8364
IS  - 705
ER  - 
TY  - GEN
A1  - Randall, Matthew J.
A1  - Jüngel, Astrid
A1  - Rimann, Markus
A1  - Wuertz-Kozak, Karin
T1  - Advances in the biofabrication of 3D skin in vitro
BT  - healthy and pathological models
T2  - Postprints der Universität Potsdam : Humanwissenschaftliche Reihe
N2  - The relevance for in vitro three-dimensional (3D) tissue culture of skin has been present for almost a century. From using skin biopsies in organ culture, to vascularized organotypic full-thickness reconstructed human skin equivalents, in vitro tissue regeneration of 3D skin has reached a golden era. However, the reconstruction of 3D skin still has room to grow and develop. The need for reproducible methodology, physiological structures and tissue architecture, and perfusable vasculature are only recently becoming a reality, though the addition of more complex structures such as glands and tactile corpuscles require advanced technologies. In this review, we will discuss the current methodology for biofabrication of 3D skin models and highlight the advantages and disadvantages of the existing systems as well as emphasize how new techniques can aid in the production of a truly physiologically relevant skin construct for preclinical innovation.
T3  - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 680 
KW  - 3D tissue model
KW  - skin
KW  - in vitro
KW  - bioprinting
KW  - electrospinning
KW  - skin disease
KW  - biofabrication
KW  - preclinical testing
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-468844
SN  - 1866-8364
IS  - 680
ER  - 
TY  - GEN
A1  - Krupkova, Olga
A1  - Smolders, Lucas
A1  - Wuertz-Kozak, Karin
A1  - Cook, James
A1  - Pozzi, Antonio
T1  - The pathobiology of the meniscus
BT  - a comparison between the human and dog
T2  - Frontiers in Veterinary Science
N2  - 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.
T3  - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 677 
KW  - meniscus
KW  - inflammation
KW  - oxidative stress
KW  - pain
KW  - dog
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-460868
SN  - 1866-8364
IS  - 677
ER  - 
TY  - JOUR
A1  - Wuertz-Kozak, Karin
A1  - Roszkowski, Martin
A1  - Cambria, Elena
A1  - Block, Andrea
A1  - Kuhn, Gisela A.
A1  - Abele, Thea
A1  - Hitzl, Wolfgang
A1  - Drießlein, David
A1  - Müller, Ralph
A1  - Rapp, Michael Armin
A1  - Mansuy, Isabelle M.
A1  - Peters, Eva M. J.
A1  - Wippert, Pia-Maria
T1  - Effects of Early Life Stress on Bone Homeostasis in Mice and Humans
JF  - International Journal of Molecular Sciences
N2  - Bone pathology is frequent in stressed individuals. A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (μCT), metabolism (qPCR/ELISA), and neuronal stress mediator expression (qPCR) and compared with a sample of depressive patients with or without early life stress by analyzing bone mineral density (BMD) (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.
KW  - psychosocial stress
KW  - bone pathologies
KW  - osteoporosis
KW  - bone mineral density
KW  - childhood
KW  - neuroendocrine
Y1  - 2020
U6  - https://doi.org/10.3390/ijms21186634
SN  - 1422-0067
VL  - 21
IS  - 18
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -