Brigitte Bau
University of Erlangen-Nuremberg
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Featured researches published by Brigitte Bau.
Matrix Biology | 2003
Thomas Aigner; Pia M. Gebhard; Erik Schmid; Brigitte Bau; Vincent R. Harley; Ernst Pöschl
Anabolic activity is a crucial activity of articular chondrocytes and its failure is one major reason of osteoarthritic cartilage degeneration. The intracellular factors responsible for the increase or decrease of anabolic activity of articular chondrocytes remain largely unknown. A recent candidate, the transcription factor SOX9, has elicited much interest as it is suggested to be a central factor in chondrocytic differentiation during development, including collagen type II (COL2A1) expression, the major anabolic gene product of chondrocytes. Here we show that normal adult human articular chondrocytes in vivo contain high SOX9 mRNA levels, which are decreased in osteoarthritic cartilage. Surprisingly, no positive correlation between SOX9 and COL2A1 expression was observed--to the contrary, the expression of COL2A1 was significantly increased in the diseased cells. Immunolocalization confirmed the presence of SOX9 protein in normal and osteoarthritic chondrocytes without showing significant differences in both SOX9 quantity and subcellular localization in osteoarthritic compared to normal cartilage tissue. Interestingly, laser scanning confocal microscopy showed that the subcellular distribution of SOX9 in adult chondrocytes was not restricted to the nucleus as observed in fetal chondrocytes, but was also detected within the cytoplasm, with no differences in subcellular SOX9 distribution between normal and OA cartilage. This is consistent with the lack of positive correlation between SOX9 and COL2A1 expression in adult articular chondrocytes. Also, no positive correlation between SOX9 and COL2A1 expression was observed in vitro after challenge of chondrocytes with Il-1beta, which is a strong (negative) regulator of COL2A1 expression, or with IGF-I, which stimulates COL2A1 expression. These results suggest that SOX9 is not the key regulator of COL2A1 promoter activity in human adult articular chondrocytes. However, SOX9 might still be involved in maintaining the chondrocytic phenotype in normal and osteoarthritic cartilage.
Journal of Orthopaedic Research | 2003
Pia M. Gebhard; Angelika Gehrsitz; Brigitte Bau; Stephan Söder; Wolfgang Eger; Thomas Aigner
Many studies have shown increased anabolic activity in osteoarthritic cartilage and have suggested changes in the cellular phenotypes of articular chondrocytes. Most of these studies relied on non‐quantitative technologies, which did not allow the estimation of the relative importance of the different differentiation phenomena. In the present study, we developed and used quantitative PCR assays for collagen types I, II(total), IIA, III, and X as marker genes indicating cellular synthetic activity (collagen type II) as well as differentiation pattern of chondrocytes (collagen types I, IIA, III, and X) and quantified these genes in normal, early degenerative, and late stage osteoarthritic cartilage in parallel.
Rheumatology International | 2006
Zhiyong Fan; Huiqing Yang; Brigitte Bau; Stephan Söder; Thomas Aigner
Interleukin-1ß is a pro-inflammatory cytokine that causes anti-anabolic and catabolic effects on articular chondrocytes via four major signaling pathways. In this study, we investigated the role of these pathways for the repression of collagen type II, and induction of MMP-1 and -13 by Il-1ß. Human adult chondrocytes were stimulated with IL-1β together with selective inhibitors of the ERK, JNK, p38, and NFκB pathways. Inhibitors of ERK and NFκB could significantly block the induction of MMP-1 and -13 (p<0.05) and the repression of collagen type II (p<0.01). The inhibitor for p38 MAPK was able to block partially MMP-1 and -13 up-regulation (p<0.01), but did not significantly inhibit collagen type II repression. Our data suggest that ERK and NFkB pathways are particularly important for IL-1β regulating collagen type II and MMP-1 and -13 expression and that p38, but not JNK is additionally involved in MMP-1 and -13 induction.
Journal of Bone and Mineral Research | 2002
Brigitte Bau; Jochen Haag; Erik Schmid; Martina Kaiser; Pia M. Gebhard; Thomas Aigner
Bone morphogenetic proteins (BMPs) are supposed to be important for cartilage matrix anabolism. In this study, we investigated whether the intracellular mediators of BMP activity, Smads 1, 4, 5, and 8, are expressed in normal human articular chondrocytes in vivo and in vitro and whether alterations in expression and distribution pattern are found in osteoarthritic cartilage or in vitro after stimulation with interleukin (IL)‐1, because down‐regulation of these mediators could be responsible for the decrease of anabolic activity in osteoarthritic cartilage. RNA was isolated from normal and osteoarthritic human knee cartilage and analyzed by (quantitative) polymerase chain reaction (PCR) technology. Articular chondrocytes were cultured in alginate beads and short‐term high‐density monolayer cultures with and without stimulation by IL‐1. In addition, immunolocalization of the receptor‐associated Smads (R‐Smads) was performed on sections of normal and diseased articular cartilage. Reverse‐transcription (RT)‐PCR analysis showed a moderate expression of all Smads investigated in normal, early degenerative, and late stage osteoarthritic cartilage. Immunolocalization detected the R‐Smads in most chondrocytes on the protein level in all specimen groups investigated. In vitro, the Smads were also expressed and partly up‐regulated by Il‐1β in alginate bead culture. Of note, for Smad 1, two truncated splice variants were expressed by articular chondrocytes missing exon 4 as well as exons 3 and 4. Our study showed that BMP‐receptor Smads 1, 5, and 8 as well as common Smad (C‐Smad) 4 are expressed and present in human normal and osteoarthritic articular chondrocytes corroborating the importance of BMPs and BMP signaling for articular cartilage. This study is the first to describe splicing variants for Smad 1. Smads 1, 4, and 5 are up‐regulated in vitro by Il‐1β, suggesting a linkage of the Il‐1 and BMP‐signaling pathways within the chondrocytes. None of the Smads were grossly up‐ or down‐regulated in osteoarthritic chondrocytes, suggesting that differences in overall expression levels of the investigated Smad proteins are not relevant for metabolic activity of articular chondrocytes in vivo.
Methods in molecular medicine | 2004
Audrey McAlinden; Jochen Haag; Brigitte Bau; Pia M. Gebhard; Thomas Aigner
Unlike any other technology in molecular biology, the polymerase chain reaction (PCR) has changed the technological armamentarium of molecular scientists working on cartilage, in terms of outstanding sensitivity and accuracy. Four approaches to determine mRNA expression levels by PCR amplification of specific cDNA sequences are currently in use and are discussed in this chapter: conventional PCR with end-point determination, conventional PCR in the logarithmic amplification phase, conventional PCR using internal competitive DNA fragments, and real-time PCR as offered by TaqMan technology and others. The determination of mRNA expression levels by real-time quantitative PCR appears to be the most reliable method for accurate determination of gene expression levels within cartilage and cultured chondrocytes, as in other tissues and cell types. This technology offers outstanding sensitivity and accuracy in terms of determination of the amount of cDNA molecules. However, this method cannot account for factors such as efficiency of RNA isolation and reverse transcription conditions. Thus, normalization of the acquired data is required, with all its limitations as described.
Arthritis & Rheumatism | 2002
Brigitte Bau; Pia M. Gebhard; Jochen Haag; Thomas Knorr; Eckart Bartnik; Thomas Aigner
Arthritis & Rheumatism | 2005
Zhiyong Fan; Brigitte Bau; Huiqing Yang; Stephan Soeder; Thomas Aigner
Cytokine | 2004
Zhiyong Fan; Brigitte Bau; Huiqing Yang; Thomas Aigner
Arthritis & Rheumatism | 2004
Martina Kaiser; Jochen Haag; Stephan Söder; Brigitte Bau; Thomas Aigner
The Journal of Rheumatology | 2004
Lydia Wachsmuth; Brigitte Bau; Zhiyong Fan; Anja Pecht; Nicole Gerwin; Thomas Aigner