Martin Stradner | Medical University of Graz (original) (raw)

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Papers by Martin Stradner

Journal of orthopaedic research : official publication of the Orthopaedic Research Society, Jan 21, 2015

Formation of chondrocyte clusters is not only a morphological sign of osteoarthritis but it is al... more Formation of chondrocyte clusters is not only a morphological sign of osteoarthritis but it is also observed in cell culture. Active locomotion of chondrocytes is controlled by integrins in vitro. Integrins bind to Laminin-A4 (LAMA4), a protein that is highly expressed in vivo in clusters of hypertrophic chondrocytes. We tested if LAMA4 is relevant for cluster formation. Human chondrocytes were cultured in a 2D matrigel model and treated with different concentrations of a monoclonal inhibitory anti-LAMA4-antibody. Migration and cluster formation was analysed using live cell imaging technique. Full genome gene expression analysis was performed to assess the effect of LAMA4 inhibition. The data set were screened for genes relevant to cell motility. F-actin staining was performed to document cytoskeletal changes. Anti-LAMA4 treatment significantly reduced the rate of cluster formation in human chondrocytes. Cells changed their surface morphology and exhibited fewer protrusions. Express...

Wiener klinische Wochenschrift

Annals of the Rheumatic Diseases

Background and objectives Although B cell depletion with rituximab (RTX) is an effective treatmen... more Background and objectives Although B cell depletion with rituximab (RTX) is an effective treatment strategy in rheumatoid arthritis (RA) one third of patients does not achieve low disease activity after rituximab. We have previously reported that the frequency of circulating plasmablasts is a negative predictor of RTX response; however, additional biomarkers could be helpful to better tailor treatment strategies to RA patients. In the present study we investigated, whether other lymphocyte subsets or combinations thereof are useful predictors of a clinical response to RTX treatment.

Annals of the Rheumatic Diseases, 2014

Osteoarthritis and Cartilage, 2011

International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, 2014

Exposure to increased environmental temperatures is commonly used as a non-pharmacological treatm... more Exposure to increased environmental temperatures is commonly used as a non-pharmacological treatment modality in ankylosing spondylitis (AS). We aimed to investigate systemic immunological effects of moderate whole body hyperthermia in patients with AS compared to healthy control subjects. Ten healthy control subjects and six AS patients underwent whole body hyperthermia treatment with 38.7-39 °C body core temperature over 60 min. Numbers of polymorphonuclear leucocytes and lymphocyte subsets, plasma concentrations of several acute phase reactants and cytokines, and gene expression levels of toll-like receptor 4 (TLR-4), interleukin 10 (IL-10) and heat shock protein beta 1 (HSPB1) were determined during and up to 24 h after treatment. TLR-4, IL-10 and HSPB1 gene expression increased significantly up to 3 h post treatment, with an earlier, higher and more pronounced increase of IL-10 in patients with AS. An increase of natural killer cells and CD8+ T lymphocytes was noted during acti...

Journal of Orthopaedic Research, 2014

The development of osteoarthritis (OA) depends on genetic and environmental factors, which influe... more The development of osteoarthritis (OA) depends on genetic and environmental factors, which influence the biology of the chondrocyte via epigenetic regulation. Changes within the epigenome might lead the way to discovery of new pathogenetic pathways. We performed a genome-wide methylation screening to identify potential differences between paired mild and severe osteoarthritic human cartilage. Sixteen female patients suffering from OA underwent total knee joint replacement. Cartilage specimens collected from corresponding macroscopically undamaged and from damaged areas were processed for DNA extraction and histology to evaluate the histological grading of the disease. Paired specimens were analysed for the methylation status of the whole genome using human promoter microarrays (Agilent, Santa Clara, CA). Selected target genes were then validated via methylation-specific qPCR. One thousand two hundred and fourteen genetic targets were identified differentially methylated between mild and severe OA. One thousand and seventy of these targets were found hypermethylated and 144 hypomethylated. The descriptive analysis of these genes by Gene Ontology (GO), KEGG pathway and protein domain analyses points to pathways of development and differentiation. We identified a list of genes which are differently methylated in mild and severe OA cartilage. Within the pathways of growth and development new therapeutic targets might arise by improving our understanding of pathogenetic mechanisms in OA.

Cytokine, 2015

Invariant Natural Killer T (iNKT) cells represent a population of innate T lymphocytes which act ... more Invariant Natural Killer T (iNKT) cells represent a population of innate T lymphocytes which act as &amp;#39;first-responders&amp;#39; to infection. While they have long been considered a versatile cell, capable of secretion of multiple cytokines upon activation, recent evidence now indicates that distinct lineages of iNKT cells with unique transcriptional and cytokine profiles exist in different peripheral tissue and as such represent &amp;#39;fine-tuning&amp;#39; of these cells, which act as mediators between the innate and adaptive immune systems. Here we discuss the molecules regulating the differentiation of iNKT cell lineages, the transcription factors associated with their development, and the role of E protein transcription factors and their negative regulators the Id proteins, as these cells develop from immature progenitor cells to terminally differentiated cells in peripheral tissue.

Osteoarthritis Cartilage, 2008

Sphingosine-1-phosphate (S1P) is a messenger molecule, with important functions in inflammation a... more Sphingosine-1-phosphate (S1P) is a messenger molecule, with important functions in inflammation and wound healing. The present study was performed to elucidate a possible role of S1P signaling in articular chondrocytes. Human and bovine primary chondrocytes were cultured in monolayer. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to detect S1P receptor mRNA. Proliferation of S1P stimulated chondrocytes was measured by 3H-thymidine uptake. Supernatants of cultured bovine chondrocytes stimulated with S1P alone or in combination with interleukin-1beta (IL-1beta) were tested for nitric oxide (NO) formation and expression of inducible nitric oxide synthase (iNOS). Matrixmetalloprotease-13 (MMP-13) and aggrecanase-1 (ADAMTS-4) were evaluated using real-time PCR. Glycosaminoglycan (GAG) loss from bovine cartilage explants was evaluated using the dimethylene blue method. S1P1, S1P2 and S1P3 but not S1P4 and S1P5 receptor mRNA were detected in human and bovine chondrocytes. S1P dose dependently induced proliferation in bovine and human chondrocytes. S1P significantly reduced NO formation and iNOS mRNA and protein expression, both in un-stimulated and IL-1beta stimulated bovine chondrocytes. Furthermore, S1P dose dependently inhibited IL-1beta induced expression of ADAMTS-4 and MMP-13 and diminished IL-1beta mediated GAG depletion from cartilage explants. These results suggest that S1P provides an anti-catabolic signal in articular chondrocytes.

$Research paper thumbnail of Proliferation analysis of the growth plate after diaphyseal midshaft fracture by 5′-bromo-2′-deoxy-uridine$

Virchows Archiv, 2010

Both stimulative and inhibitory growth disturbances may occur after a fracture during the growth ... more Both stimulative and inhibitory growth disturbances may occur after a fracture during the growth period. The exact mechanism responsible for stimulative growth disturbances in the immature skeleton is unexplained. It&amp;amp;amp;amp;amp;#39;s possible that chondrocyte proliferation leads to overgrowth. This study investigates the effect of a fracture on the proliferation of chondrocytes at the nearby growth plate and its effect on the contra-lateral leg. Fifty-six 1-month-old Sprague-Dawley rats (weight, 100-120 g) were randomised to either an experimental or a control group. A closed mid-diaphyseal tibial fracture was produced in all animals of the experimental group using a standardised technique. On day 3, 10, 14 and 29 of the experiment, the rats were euthanised and their tibial growth plates were subjected to histological analysis. 5&amp;amp;amp;amp;amp;#39;-Bromo-2&amp;amp;amp;amp;amp;#39;-deoxy-uridine labelling was used for the quantitative analysis of chondrocyte proliferation. Safranin O staining provided the histological overview for the subsequent analysis of BrdU-labelling. Immunohistochemical analysis showed increased proliferation of chondrocytes in the growth plates of broken bones during fracture healing. This proliferation peaked on day 3 post-fracture and then reduced gradually until day 29. No increase in the rate of proliferation was observed on the contra-lateral limbs of the animals in the experimental group. Following a diaphyseal fracture of the tibia, the growth plates located next to the fracture react with increased cell proliferation. This proliferation was not observed in the contra-lateral uninjured tibia. This investigation shows that the post-traumatic length discrepancy is a local biological process at the growth plate brought about by the fracture.

Scandinavian Journal of Rheumatology, 2011

Osteoarthritis and Cartilage, 2009

Osteoarthritis and Cartilage, 2008

Osteoarthritis and Cartilage, 2010