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...

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...

ba0004oc15 | (1) | ICCBH2015

Osseous side effects on the growing skeleton exerted by tyrosine kinase inhibitor treatment: data observed in pediatric patients with chronic myeloid leukemia in comparison to a juvenile rat model

Tauer Josephine T , Hofbauer Lorenz C , Erben Reinhold G , Suttorp Meinolf

Background: The tyrosine kinase inhibitor (TKI) imatinib is applied as front-line treatment in adult and pediatric patients with chronic myeloid leukemia (CML) in order to selectively inhibit the causative oncogenic BCR-ABL1 tyrosine kinase. However, TKIs exhibit off-target effects on further kinases involved in the regulation of bone metabolism. As consequence, pediatric patients display longitudinal growth retardation while on imatinib treatment. As CML is a rare disease in ...

ba0005oc2.2 | Bone mass and bone strength Wnt signalling | ECTS2016

Deletion of Dickkopf-1 in osteoblasts or osteocytes increases bone volume in female mice

Thiele Sylvia , Baschant Ulrike , Thiele Stefanie , Niehrs Christof , Bonewald Lynda , Hofbauer Lorenz C , Rauner Martina

Osteoporosis is a frequent disease leading to an increased risk of fractures caused by a systemic impairment of bone mass, strength, and microarchitecture. Given the emerging role of the Wnt signaling pathway in bone biology, we focused on the function of the important Wnt inhibitor dickkopf-1 (Dkk-1) and examined how the deletion of Dkk-1 solely in osteoblasts or osteocytes influences bone homeostasis. Therefore, we used the Cre-LoxP recombination system and crossed Dkk-1-flo...

ba0005p106 | Cancer and bone: basic, translational and clinical | ECTS2016

The Rho GTPases RhoA and CDC42 mediate apoptosis by a combination of statins and zoledronic acid in human bone-seeking breast cancer cells

Gobel Andy , Thiele Stefanie , Browne Andrew J , Rauner Martina , Hofbauer Lorenz C , Rachner Tilman D

Breast cancer is the most frequent malignancy in women and frequently results in osteolytic bone metastases. Amino-bisphosphonates are a standard bone protective therapy and, similarly to statins, inhibit the mevalonate pathway that is crucial for posttranslational protein modifications (farnesylation and geranylation). Direct anti-tumor effects of amino-bisphosphonates and statins have been suggested but high concentrations are necessary to achieve meaningful effects. Our stu...

ba0005p110 | Cancer and bone: basic, translational and clinical | ECTS2016

Role of the receptors FZD8 and RYK in mediating the anti-tumor effects of WNT5A on prostate cancer cells

Thiele Stefanie , Gobel Andy , Hippauf Sandra , Rachner Tilman , Rauner Martina , Hofbauer Lorenz C

Wnt proteins and their cognate receptors play a significant role in malignant diseases, in particular in prostate cancer (PCa). We previously showed that WNT5A inhibits PCa cell proliferation and induces apoptosis in vitro, leading to reduced PCa growth in vivo. However, the involved receptors remain unknown. Here, we determine the role of two Wnt receptors (FZD8, RYK) and their influence on the WNT5A-induced effects on PCa cells.The ex...

ba0001oc2.2 | Bone quality and fracture repair - animal models | ECTS2013

Intermittent human parathyroid hormone (1–84) treatment improves bone mass and bone defect healing in rats with type 2 diabetes mellitus

Hamann Christine , Picke Ann-Kristin , Rauner Martina , Bernhardt Ricardo , Campbell Graeme , Gluer Claus-Christian , Hofbauer Lorenz C

The pathogenesis of skeletal fragility in diabetes mellitus is poorly defined and efficient therapies are limited. Zucker diabetic fatty (ZDF) rats with type 2 diabetes mellitus display low bone mass and delayed bone defect healing. We tested whether intermittent treatment with human parathyroid hormone 1–84 (PTH) increases bone mass and bone defect regeneration in diabetic rats.A subcritical gap defect was created at the femur of 10 weeks old diabe...