9 results on '"Jahr, Holger"'
Search Results
2. Nuclear factor erythroid 2–related factor 2 (Nrf2) deficiency causes age-dependent progression of female osteoporosis
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Kubo, Yusuke, Gonzalez, Jesus Abraham Herrera, Beckmann, Rainer, Weiler, Marek, Pahlavani, Helda, Saldivar, Mauricio Cruz, Szymanski, Katharina, Rosenhain, Stefanie, Fragoulis, Athanassios, Leeflang, Sander, Slowik, Alexander, Gremse, Felix, Wolf, Michael, Mirzaali, Mohammad Javad, Zadpoor, Amir Abbas, Wruck, Christoph Jan, Pufe, Thomas, Tohidnezhad, Mersedeh, and Jahr, Holger
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- 2022
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3. Effect of platelet mediator concentrate (PMC) on Achilles tenocytes: an in vitro study.
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Arslan, Esra, Nellesen, Thomas, Bayer, Andreas, Prescher, Andreas, Lippross, Sebastian, Nebelung, Sven, Jahr, Holger, Jaeger, Christine, Huebner, Wolf Dietrich, Fischer, Horst, Stoffel, Marcus, Shakibaei, Mehdi, Pufe, Thomas, and Tohidnezhad, Mersedeh
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BLOOD platelets ,PATHOLOGICAL physiology ,TENDON injuries ,GROWTH factors ,CYTOKINES ,POLYMERASE chain reaction ,PROTEIN metabolism ,THERAPEUTIC use of proteins ,ACHILLES tendon ,ANIMAL experimentation ,BIOLOGICAL models ,BONE morphogenetic proteins ,CELL culture ,CELL differentiation ,CELL physiology ,COLLAGEN ,ENZYME-linked immunosorbent assay ,IMMUNOHISTOCHEMISTRY ,MEMBRANE proteins ,MICE ,REGENERATION (Biology) ,WOUND healing ,VASCULAR endothelial growth factors ,HUMAN research subjects ,GENE expression profiling ,METABOLISM ,THERAPEUTICS - Abstract
Background: Although there are many studies discussing the etiological and pathological factors leading to both, acute and chronic tendon injuries, the pathophysiology of tendon injuries is still not clearly understood. Although most lesions are uncomplicated, treatment is long and unsatisfactory due to the poor vascularity of tendon tissue. Platelet mediator concentrate (PMC) contains many growth factors derived from platelets, which can promote wound healing. In this study we investigate the effects of PMC on tenocyte proliferation and differentiation in order to provide an experimental basis for tissue regeneration strategies and to develop new treatment concepts.Methods: Using enzyme linked immunosorbent assay (ELISA) we were able to quantify the several growth factors and cytokines found in PMC. Tenocytes were isolated both from human and from mouse Achilles tendons and stimulated with PMC. CyQuant® and Cell Titer Blue® assays were carried out to analyze tendon growth and viability at different concentrations of PMC. Real time RT-PCR was used to analyze tenocyte gene expression with or without PMC treatment. Immunohistochemistry was carried out to detect the tenocyte-specific antibody tenomodulin (TNMD) and scleraxis (SCX).Results: We were able to detect numerous mediators such as platelet derived growth factor BB (PDGF-BB), interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF-α), transforming growth factor beta 1 (TGF-ß1), and bone morphogenetic proteins 2, 4 and 7 (BMP-4, BMP-2, BMP-7) in PMC. It was possible to show a positive effect of PMC on human tendon cell growth and viability in a dose-dependent manner. Furthermore, PMC treatment led to induction of gene expression of scleraxis (SCX), type I collagen A 1 (Col1A1) and TNMD by tenocytes.Conclusions: We suggest that the use of autologous PMC may be a suitable addition to conventional tendon therapy that is capable of increasing and optimizing tendon healing and reducing the risk of recurrence. [ABSTRACT FROM AUTHOR]- Published
- 2016
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4. Abrasion arthroplasty increases mesenchymal stem cell content of postoperative joint effusions.
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Beckmann, Rainer, Lippross, Sebastian, Hartz, Claudia, Tohidnezhad, Mersedeh, Ferreira, Mónica S. Ventura, Neuss-Stein, Sabine, Seekamp, Andreas, Nebelung, Sven, Kweider, Nisreen, Rath, Björn, Jahr, Holger, Pufe, Thomas, and Varoga, Deike J.
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ARTHROPLASTY ,JOINT surgery ,MESENCHYMAL stem cells ,CHONDROITIN ,COLLAGEN - Abstract
Background: Abrasion arthroplasty (AAP) is a procedure by which intrinsic cartilage healing is believed to be stimulated. Although clinically accepted for degenerative and traumatic cartilage lesions scientific evidence at a molecular level that proves the effect of AAP is scarce.Method: Mononuclear cells were extracted from postoperative joint effusions 21.5 h post AAP and simple debridement of cartilage lesions. Luminex, ELISA and FACS experiments were performed. Immunohistochemical stainings of cell cultures for cartilage markers were used to confirm the findings.Results: Postoperative joint effusions after AAP showed increased contents of Mononuclear cells compared to Arthroscopic Chondroplasty (ACP). BMP-4 and IGF were increased in AAP as complared to ACP. Mononuclear cells isolated after AAP express the MSC markers CD 73, CD 105, CD 90, CD 44 and are CD34 negative. Chondrogenic differentiation was demonstrated by positive staining for Sox9, collagen II, proteoglycan, chondroitin-4-sulfate.Conclusion: Our results support the clinical application of AAP as a procedure that enhances cartilage repair as an alternative to far more complex procedures that have gained popularity. Furthermore the data presented supports clinical investigations that recommend not to use suction drainage as by this procedure a considerable amount of the regeneratory potential of postoperative joint effusions might be extracted. [ABSTRACT FROM AUTHOR]- Published
- 2015
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5. GREM1, FRZB and DKK1 mRNA levels correlate with osteoarthritis and are regulated by osteoarthritis-associated factors.
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Leijten, Jeroen C. H., Bos, Steffan D., Landman, Ellie B. M., Georgi, Nicole, Jahr, Holger, Meulenbelt, Ingrid, Post, Janine N., van Blitterswijk, Clemens A., and Karperien, Marcel
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- 2013
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6. Stimulation of osteogenic differentiation in human osteoprogenitor cells by pulsed electromagnetic fields: an in vitro study.
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Jansen, Justus H. W., van der Jagt, Olav P., Punt, Bas J., Verhaar, Jan A. N., van Leeuwen, Johannes P. T. M., Weinans, Harrie, and Jahr, Holger
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ELECTROMAGNETIC fields ,STEM cells ,OSTEOSARCOMA ,DNA ,BONE injuries - Abstract
Background: Although pulsed electromagnetic field (PEMF) stimulation may be clinically beneficial during fracture healing and for a wide range of bone disorders, there is still debate on its working mechanism. Mesenchymal stem cells are likely mediators facilitating the observed clinical effects of PEMF. Here, we performed in vitro experiments to investigate the effect of PEMF stimulation on human bone marrow-derived stromal cell (BMSC) metabolism and, specifically, whether PEMF can stimulate their osteogenic differentiation. Methods: BMSCs derived from four different donors were cultured in osteogenic medium, with the PEMF treated group being continuously exposed to a 15 Hz, 1 Gauss EM field, consisting of 5-millisecond bursts with 5-microsecond pulses. On culture day 1, 5, 9, and 14, cells were collected for biochemical analysis (DNA amount, alkaline phosphatase activity, calcium deposition), expression of various osteoblast-relevant genes and activation of extracellular signal-regulated kinase (ERK) signaling. Differences between treated and control groups were analyzed using the Wilcoxon signed rank test, and considered significant when p < 0.05. Results: Biochemical analysis revealed significant, differentiation stage-dependent, PEMF-induced differences: PEMF increased mineralization at day 9 and 14, without altering alkaline phosphatase activity. Cell proliferation, as measured by DNA amounts, was not affected by PEMF until day 14. Here, DNA content stagnated in PEMF treated group, resulting in less DNA compared to control. Quantitative RT-PCR revealed that during early culture, up to day 9, PEMF treatment increased mRNA levels of bone morphogenetic protein 2, transforming growth factor-beta 1, osteoprotegerin, matrix metalloproteinase-1 and -3, osteocalcin, and bone sialoprotein. In contrast, receptor activator of NF-κB ligand expression was primarily stimulated on day 14. ERK½ phosphorylation was not affected by PEMF stimulation. Conclusions: PEMF exposure of differentiating human BMSCs enhanced mineralization and seemed to induce differentiation at the expense of proliferation. The osteogenic stimulus of PEMF was confirmed by the up-regulation of several osteogenic marker genes in the PEMF treated group, which preceded the deposition of mineral itself. These findings indicate that PEMF can directly stimulate osteoprogenitor cells towards osteogenic differentiation. This supports the theory that PEMF treatment may recruit these cells to facilitate an osteogenic response in vivo. [ABSTRACT FROM AUTHOR]
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- 2010
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7. Intrinsic differentiation potential of adolescent human tendon tissue: an in-vitro cell differentiation study.
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de Mos, Marieke, Koevoet, Wendy J. L. M., Jahr, Holger, Verstegen, Monique M. A., Heijboer, Marinus P., Kops, Nicole, van Leeuwen, Johannes P. T. M., Weinans, Harrie, Verhaar, Jan A. N., and van Osch, Gerjo J. V. M.
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TENDONS ,GLYCOSAMINOGLYCANS ,CELL differentiation ,TENDINOSIS ,IMMUNOHISTOCHEMISTRY ,FIBROBLASTS ,PATHOLOGICAL physiology - Abstract
Background: Tendinosis lesions show an increase of glycosaminoglycan amount, calcifications, and lipid accumulation. Therefore, altered cellular differentiation might play a role in the etiology of tendinosis. This study investigates whether adolescent human tendon tissue contains a population of cells with intrinsic differentiation potential. Methods: Cells derived from adolescent non-degenerative hamstring tendons were characterized by immunohistochemistry and FACS-analysis. Cells were cultured for 21 days in osteogenic, adipogenic, and chondrogenic medium and phenotypical evaluation was carried out by immunohistochemical and qPCR analysis. The results were compared with the results of similar experiments on adult bone marrow-derived stromal cells (BMSCs). Results: Tendon-derived cells stained D7-FIB (fibroblast-marker) positive, but α-SMA (marker for smooth muscle cells and pericytes) negative. Tendon-derived cells were 99% negative for CD34 (endothelial cell marker), and 73% positive for CD105 (mesenchymal progenitor-cell marker). In adipogenic medium, intracellular lipid vacuoles were visible and tendon-derived fibroblasts showed upregulation of adipogenic markers FABP4 (fatty-acid binding protein 4) and PPARG (peroxisome proliferative activated receptor γ). In chondrogenic medium, some cells stained positive for collagen 2 and tendon-derived fibroblasts showed upregulation of collagen 2 and collagen 10. In osteogenic medium Von Kossa staining showed calcium deposition although osteogenic markers remained unaltered. Tendon-derived cells and BMCSs behaved largely comparable, although some distinct differences were present between the two cell populations. Conclusion: This study suggests that our population of explanted human tendon cells has an intrinsic differentiation potential. These results support the hypothesis that there might be a role for altered tendon-cell differentiation in the pathophysiology of tendinosis. [ABSTRACT FROM AUTHOR]
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- 2007
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8. HDACi and Nrf2: not from alpha to omega but from acetylation to OA.
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Jahr, Holger
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- 2015
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9. Physiological tonicity improves human chondrogenic marker expression through nuclear factor of activated T-cells 5 in vitro.
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van der Windt AE, Haak E, Das RH, Kops N, Welting TJ, Caron MM, van Til NP, Verhaar JA, Weinans H, and Jahr H
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- Aggrecans metabolism, Cartilage, Articular cytology, Cell Differentiation drug effects, Cell Proliferation drug effects, Cell Survival drug effects, Cells, Cultured, Chondrocytes cytology, Collagen Type I metabolism, Collagen Type II metabolism, Humans, NFATC Transcription Factors genetics, Osmolar Concentration, Phenotype, Cartilage, Articular drug effects, Cartilage, Articular metabolism, Chondrocytes drug effects, Chondrocytes metabolism, Hypertonic Solutions pharmacology, NFATC Transcription Factors metabolism
- Abstract
Introduction: Chondrocytes experience a hypertonic environment compared with plasma (280 mOsm) due to the high fixed negative charge density of cartilage. Standard isolation of chondrocytes removes their hypertonic matrix, exposing them to nonphysiological conditions. During in vitro expansion, chondrocytes quickly lose their specialized phenotype, making them inappropriate for cell-based regenerative strategies. We aimed to elucidate the effects of tonicity during isolation and in vitro expansion on chondrocyte phenotype., Methods: Human articular chondrocytes were isolated and subsequently expanded at control tonicity (280 mOsm) or at moderately elevated, physiological tonicity (380 mOsm). The effects of physiological tonicity on chondrocyte proliferation and chondrogenic marker expression were evaluated. The role of Tonicity-responsive Enhancer Binding Protein in response to physiological tonicity was investigated using nuclear factor of activated T-cells 5 (NFAT5) RNA interference., Results: Moderately elevated, physiological tonicity (380 mOsm) did not affect chondrocyte proliferation, while higher tonicities inhibited proliferation and diminished cell viability. Physiological tonicity improved expression of chondrogenic markers and NFAT5 and its target genes, while suppressing dedifferentiation marker collagen type I and improving type II/type I expression ratios >100-fold. Effects of physiological tonicity were similar in osteoarthritic and normal (nonosteoarthritic) chondrocytes, indicating a disease-independent mechanism. NFAT5 RNA interference abolished tonicity-mediated effects and revealed that NFAT5 positively regulates collagen type II expression, while suppressing type I., Conclusions: Physiological tonicity provides a simple, yet effective, means to improve phenotypical characteristics during cytokine-free isolation and in vitro expansion of human articular chondrocytes. Our findings will lead to the development of improved cell-based repair strategies for chondral lesions and provides important insights into mechanisms underlying osteoarthritic progression.
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- 2010
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