A5101857484- Bone Metabolism and Diseases
- Bone health and treatments
- Cytokine Signaling Pathways and Interactions
- Wnt/β-catenin signaling in development and cancer
- NF-κB Signaling Pathways
- Protein Kinase Regulation and GTPase Signaling
- Rheumatoid Arthritis Research and Therapies
- Immune Response and Inflammation
- Connective tissue disorders research
- T-cell and B-cell Immunology
- Melanoma and MAPK Pathways
- Nuclear Structure and Function
- Microtubule and mitosis dynamics
- Adipokines, Inflammation, and Metabolic Diseases
- Genetics and Neurodevelopmental Disorders
- Immune cells in cancer
- Reproductive System and Pregnancy
- RNA Research and Splicing
- Immune Cell Function and Interaction
- Phagocytosis and Immune Regulation
- Inflammatory mediators and NSAID effects
- Genetic factors in colorectal cancer
- Peroxisome Proliferator-Activated Receptors
- Osteoarthritis Treatment and Mechanisms
- Regulation of Appetite and Obesity
Universität Hamburg
2013-2022
University Medical Center Hamburg-Eppendorf
2013-2022
Friedrich-Alexander-Universität Erlangen-Nürnberg
2008-2019
Universitätsklinikum Erlangen
2009-2019
Radiation Oncology Institute
2014
German Rheumatism Research Centre
2005-2011
Center for Rheumatology
2009
Research Institute of Molecular Pathology
1998-2005
Yale University
1997-1998
Yale Cancer Center
1998
The detailed cellular and molecular mechanisms leading to joint destruction in rheumatoid arthritis, a disease driven by proinflammatory cytokines, are still unknown. To address the question of whether osteoclasts play pivotal role this process, transgenic mice that express human TNF (hTNFtg) develop severe destructive arthritis were crossed with osteopetrotic, c-fos–deficient (c-fos–/–) completely lacking osteoclasts. resulting mutant (c-fos–/–hTNFtg) developed TNF-dependent absence All...
The detailed cellular and molecular mechanisms leading to joint destruction in rheumatoid arthritis, a disease driven by proinflammatory cytokines, are still unknown. To address the question of whether osteoclasts play pivotal role this process, transgenic mice that express human TNF (hTNFtg) develop severe destructive arthritis were crossed with osteopetrotic, c-fos–deficient (c-fos–/–) completely lacking osteoclasts. resulting mutant (c-fos–/–hTNFtg) developed TNF-dependent absence All...
Phosphorylation of the N-terminal domain Jun by kinases (JNKs) modulates transcriptional activity AP-1, a dimeric transcription factor typically composed c-Jun and c-Fos, latter being essential for osteoclast differentiation. Using mice lacking JNK1 or JNK2, we demonstrate that JNK1, but not is specifically activated osteoclast-differentiating RANKL. Activation required efficient osteoclastogenesis from bone marrow monocytes (BMMs). protects BMMs RANKL-induced apoptosis during In addition,...
Apoptotic and mitogenic stimuli activate c-Jun NH2-terminal kinases (JNKs) in T cells. Although cells express both JNK1 JNK2 isozymes, the absence of alone can result resistance to anti-CD3–induced thymocyte apoptosis defective mature cell proliferation. Similar defects proliferation, latter due reduced interleukin 2 production, are also caused by deficiency. Importantly, function was compromised Jnk1+/−Jnk2+/− double heterozygous mice, indicating that play similar roles regulating function....
We previously demonstrated the suppressive effects of regulatory T cells (Treg cells) on osteoclast differentiation in vitro. In this article, we show that blood markers bone resorption inversely correlate with amount circulating Treg healthy controls and rheumatoid arthritis patients, further suggesting may control destruction vivo. Indeed, marrow from Foxp3-transgenic (Foxp3tg) mice fully protected human TNF transgenic (hTNFtg) TNF-alpha-induced destruction, whereas Foxp3-deficient...
Costimulatory molecules CD80/CD86 suppress osteoclast differentiation by inducing indoleamine 2,3-dioxygenase.
Abstract Acute lung injury (ALI) is a severe inflammatory disease for which no specific treatment exists. As glucocorticoids have potent immunosuppressive effects, their application in ALI currently being tested clinical trials. However, the benefits of this type regimen remain unclear. Here we identify mechanism glucocorticoid action that challenges long-standing dogma cytokine repression by receptor. Contrarily, synergistic gene induction sphingosine kinase 1 ( SphK1 ) and pro-inflammatory...
Immune activation triggers bone loss. Activated T cells are the cellular link between immune and destruction. The aim of this study was to determine whether regulatory mechanisms, such as naturally occurring Treg cells, also extend their protective effects homeostasis in vivo.Bone parameters FoxP3-transgenic (Tg) mice were compared with those wild-type (WT) littermate controls. Ovariectomy performed FoxP3-Tg a model postmenopausal osteoporosis, analyzed. bones RAG-1(-/-) analyzed following...
IL-33 is a new member of the IL-1 family, which plays crucial role in inflammatory response, enhancing differentiation dendritic cells and alternatively activated macrophages (AAM). Based on evidence expression bone, we hypothesized that may shift balance from osteoclast to AAM protect bone loss. Using transgenic mice overexpressing human TNF, develop spontaneous joint inflammation cartilage destruction, show administration or an IL-33R (ST2L) agonistic Ab inhibited systemic loss,...
Wnt1 is a physiologically relevant bone-anabolic molecule that does not require the expression of Wnt co-receptor Lrp5.
Inactivation of the growth factor–regulated S6 kinase RSK2 causes Coffin-Lowry syndrome in humans, an X-linked mental retardation condition associated with progressive skeletal abnormalities. Here we show that mice lacking develop a disease, osteopenia due to impaired osteoblast function and normal osteoclast differentiation. The phenotype is decreased expression Phex, endopeptidase regulating bone mineralization. This defect probably not mediated by RSK2-dependent phosphorylation c-Fos on...
Pharmacological inhibitors have provided evidence for the key role of p38 MAPK in osteoclast differentiation and inflammation-induced bone loss. However, these block more than one four isoforms, usually p38alpha p38beta, sometimes also other kinases such as JNK3. We show this study that is main isoenzyme expressed precursors mature osteoclasts. well its downstream substrates were phosphorylated progenitors stimulated by TNF-alpha. Using Mx-cre-mediated conditional gene inactivation we...
Cripto-1 (CR-1), a recently discovered protein of the epidermal growth factor (EGF) family, was found to interact with high affinity, saturable binding site(s) on HC-11 mouse mammary epithelial cells and several different human breast cancer cell lines. This receptor exhibits specificity for CR-1, since other EGF-related peptides including EGF, transforming α, heparin-binding EGF-like factor, amphiregulin, epiregulin, betacellulin, or heregulin β1 that bind either EGF type 1 tyrosine kinases...
A-type cyclin-dependent kinases (CDKs), also known as cdc2, are central to the orderly progression of cell cycle. We made a functional Green Fluorescent Protein (GFP) fusion with CDK-A (Cdc2-GFP) and followed its subcellular localization during cycle in tobacco cells. During interphase, Cdc2-GFP protein was found both cytoplasm nucleus, where it highly resistant extraction. In premitotic cells, bright narrow equatorial band appeared on surface, resembling late preprophase band, which...
While it is well established that adenylyl cyclase and phospholipase C-β are two proximal signal effectors for the calcitonin receptor, more distal signaling pathways less characterized. G protein-coupled receptors can activate Erk1/2 by G<sub>s</sub>-, G<sub>i</sub>-, or G<sub>q</sub>-dependent pathways, depending on specific receptor cell type examined. Since couple to all three of these proteins, ability was investigated. Calcitonin induced time- concentration-dependent increases in Shc...
Inactivation of the growth factor–regulated S6 kinase RSK2 causes Coffin-Lowry syndrome in humans, an X-linked mental retardation condition associated with progressive skeletal abnormalities. Here we show that mice lacking develop a disease, osteopenia due to impaired osteoblast function and normal osteoclast differentiation. The phenotype is decreased expression Phex, endopeptidase regulating bone mineralization. This defect probably not mediated by RSK2-dependent phosphorylation c-Fos on...
During the course of different musculoskeletal diseases, joints are progressively damaged by inflammatory, infectious, or mechanical stressors, leading to joint destruction and disability. While effective strategies inhibit inflammation, such as targeted cytokine-blocking therapy, have been developed during last decade, molecular mechanisms damage still poorly understood. This study was undertaken investigate role Wnt pathway modulator R-Spondin 1 (RSpo1) in protecting bone cartilage a mouse...