Searchable abstracts of presentations at key conferences on calcified tissues

ba0003oc3.1 | Osteoclasts, gastric hormones and HIF | ECTS2014

HIF prolyl hydroxylase 2 (PHD2) controls bone homeostasis through HIF2α -- a novel player in osteohematology

Rauner Martina , Franke Kristin , Hofbauer Lorenz C , Wielockx Ben

Prolyl hydroxylase 2 (PHD2) regulates hypoxia-inducible factor α (HIFα) transcription factors and thus, erythropoietin (EPO) production. Under normoxic conditions, HIFα is constantly inactivated through hydroxylation by PHD2. Due to the embryonic lethality of PHD2 knock-out mice, its precise role in erythropoiesis and tissue homeostasis has long remained unknown. Recently, we generated a conditional knock-out (cKO) mouse lacking PHD2 in EPO-producing cells. Thes...

ba0003pp114 | Cell biology: osteoblasts and bone formation | ECTS2014

N-linked glycosylation as a critical mechanism of PTH-resistance in osteoblasts in high glucose conditions

Picke Ann-Kristin , Hamann Christine , Rauner Martina , Hofbauer Lorenz C.

Type 2 diabetes mellitus impairs bone quality and increases fracture risk. We showed that diabetic ZDF rats have low bone mass due to impaired osteoblastogenesis, which can be partially reversed with an intermittent parathyroid hormone 1–84 (PTH) therapy. It remains unclear, why PTH treatment does not fully restore osteoblast (OB) function in diabetic conditions. Here, we tested if high glucose (HG) conditions lead to a partial PTH resistance in osteoblasts. Pre-osteoblas...

ba0005p169 | Cell biology: osteoblasts and bone formation | ECTS2016

Iron deficiency increases osteoblast function via Wnt5a

Baschant Ulrike , Platzbecker Uwe , Rauner Martina , Hofbauer Lorenz

Iron overload due to hemochromatosis or chronic blood transfusions has been implicated in the development of osteoporosis. However, the impact of iron overload or iron deficiency on stromal cell functions and the underlying mechanisms are poorly defined. Since the Wnt signaling pathway is a critical regulator of bone remodelling, we aimed to analyse the effects of iron overload and iron deficiency on osteoblast function and further define the role of Wnt signaling in these pro...

ba0005lb6 | (1) | ECTS2016

Sclerostin blockade and zoledronic acid improve bone mass and strength in mice with exogenous hyperthyroidism

Tsourdi Elena , Lademann Franziska , Ominsky Michael , Hofbauer Lorenz , Rauner Martina

Hyperthyroidism in mice is associated with a low bone mass, an increased bone turnover and high serum levels of sclerostin, a potent Wnt inhibitor. Here, we explored the effects of either reducing bone turnover with bisphosphonates or increasing bone formation with neutralizing sclerostin antibodies (Scl-Ab) on bone mass and estimated strength in hyperthyroid mice.Twelve-week-old C57BL/6 male mice were rendered hyperthyroid by adding L-thy...

ba0001oc4.4 | Osteoblasts and osteocytes | ECTS2013

Glucocorticoid exposure reduces expression of sclerostin in bone marrow stromal cells

Thiele Sylvia , Rauch Alexander , Tuckermann Jan P , Hofbauer Lorenz C , Rauner Martina

Glucocorticoids (GC) are effective drugs in the treatment of inflammatory diseases, including various forms of arthritis. However, their use is limited by negative effects on bone mass and strength, resulting in increased osteoporotic fractures. Conditional knockout mice demonstrated that the GR in osteoblasts is essential for GC-dependent bone loss. Recent studies show that GC profoundly inhibit Wnt signaling by stimulating the expression of Wnt antagonists such as dickkopf-1...

ba0001pp18 | Arthritis and other joint diseases: translational and clinical | ECTS2013

Milk fat globule-epidermal growth factor 8 is a critical determinant of bone mass and alters the course of inflammation in arthritis

Sinningen Kathrin , Thiele Sylvia , Grossklaus Sylvia , Udey Mark , Hofbauer Lorenz C , Chavakis Triantafyllos , Rauner Martina

Milk fat globule-epidermal growth factor 8 (MFG-E8) is a glycoprotein that controls the engulfment of apoptotic cells and exerts anti-inflammatory effects. It has been implicated in the pathogenesis of several diseases, but its role in the bone microenvironment is still unknown. Here we tested the hypothesis that MFG-E8 also regulates bone metabolism and the development of arthritis.MFG-E8 expression was detected in mouse bones and primary murine osteobl...

ba0001pp239 | Cell biology: osteocytes | ECTS2013

Glycosaminoglycans and their sulfate derivates differentially regulate the osteocytic phenotype of murine and rat osteocyte-like cell lines

Tsourdi Elena , Salbach-Hirsch Juliane , Rauner Martina , Richter Claudia , Rachner Tilman , Hofbauer Lorenz

Introduction: Collagen and glycosaminoglycans (GAGs) such as hyaluronan (HA) and chondroitin sulfate (CS) are basic elements of bone structure and collagen-GAG composites are currently developed for a wide range of applications. Here, we report on the molecular and cellular effects of GAGs and their sulfated derivatives on osteocytes, which are fundamental orchestrators of bone remodeling.Materials and methods: The effects of native and sulfate-modified ...

ba0001pp472 | Other diseases of bone and mineral metabolism | ECTS2013

Monocytic expression of osteoclast-associated receptor is induced in atherosclerotic mice and regulated by oxidized low-density lipoprotein in vitro

Sinningen Kathrin , Rauner Martina , Al-Fakhri Nadia , Schoppet Michael , Hofbauer Lorenz

The osteoclast-associated receptor (OSCAR), primarily described as a co-stimulatory regulator of osteoclast differentiation, represents a novel link between bone metabolism and vascular biology. Previously, we identified OSCAR on endothelial cells responding to the proatherogenic factor oxidized low density lipoprotein (oxLDL). Additionally, OSCAR expression was increased in the aorta of atherogenic apoE-knock-out (apoE-KO) mice, where it was further induced by feeding a high-...

ba0003pp414 | Steroid hormones and receptors | ECTS2014

Glucocorticoids suppress inflammation in arthritis via the glucocorticoid receptor in non-hematopoietic cells

Baschant Ulrike , Culemann Stephan , Koenen Mascha , Zhou Hong , Seibel Markus , Hofbauer Lorenz , Tuckermann Jan

Owing to their anti-inflammatory effects, steroid therapy using glucocorticoids (GCs) is still part of the treatment of rheumatoid arthritis (RA), despite several severe side effects like glucocorticoid-induced osteoporosis (GIO). Until now the molecular mechanisms underlying the beneficial and side effects of GC therapy are poorly understood. GCs exert their actions via the glucocorticoid receptor (GR) that alters gene expression by either binding as a dimer to GC response el...