Searchable abstracts of presentations at key conferences on calcified tissues

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-...

ba0003pp99 | Cancer and bone: basic, translational and clinical | ECTS2014

Changes in bone mineral density and biochemical markers of bone turnover in postmenopausal women with breast cancer initiating aromatase inhibitors therapy

Luchavova Maria , Zimovjanova Martina , Zikan Vit , Pribylova Jana , Cabinakova Michaela , Petruzelka Lubos

Postmenopausal women with early stage hormone-receptor-positive breast cancer (EBC) are standardly treated with aromatase inhibitors (AIs). However, one side-effect of AIs treatment is a decrease in bone mineral density (BMD) and an increased risk of fracture. The objectives of this study were to examine: i) changes in bone formation (N-terminal propeptide of type I procollagen; PINP) and bone resorption (cross-linked C-telopeptides of bone type I collagen; CTX) markers, as we...

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...

ba0001pp105 | Calciotropic and phosphotropic hormones and mineral metabolism | ECTS2013

α2C AR KO mice present opposite bone phenotype in femur and vertebrae

Teixeira Marilia Bianca , Martins Gisele , Costa Cristiane , Brum Patricia , Gouveia Cecilia

α2C Evidences demonstrate that sympathetic nervous system (SNS) activation causes osteopenia via β2-adrenoceptor (β2-AR) signaling. In a recent study, we showed that female mice with chronic sympathetic hyperactivity due to double knockout of adrenoceptors that negatively regulate norepinephrine release, α2A-AR and α2C-AR (α2A/α2C-ARKO), present an unexpected phenoty...

ba0001pp149 | Cancer and bone: basic, translational and clinical | ECTS2013

Cytotoxicity of picocyanobacteria strains of the genera Cyanobium on osteosarcoma cells

Martins Rosario , Costa Margarida , Garcia Monica , Barros Piedade , Costa-Rodrigues Joao , Vasconcelos Vitor , Fernandes Maria

Marine cyanobacteria have been recognized as an important source of bioactive compounds. The cytotoxicity on cancer cell lines has been extensively explored and several cyanobacteria metabolites are already described as potential anticancer compounds or are considered useful templates for the design of new anticancer drugs. The majority of compounds have been isolated from filamentous or colonial cyanobacteria that growth in high densities along shores. In contrast, picoplankt...

ba0003pp145 | Cell biology: osteoblasts and bone formation | ECTS2014

Effects of strontium ranelate on the bone-like mineralized matrix produced in osteoblast cell cultures

Querido William , Campos Andrea , Ferreira Erlon Martins , Gil Rosane San , Rossi Alexandre , Farina Marcos

Strontium ranelate is a promising drug used in the treatment of osteoporosis. This drug has a unique dual effect on bone turnover, simultaneously increasing bone formation by osteoblasts (anabolic effect) and decreasing bone resorption by osteoclasts (antiresorptive effect). The goal of this study was to evaluate: i) anabolic effects of strontium ranelate on the formation of bone-like mineralized matrix in osteoblast cell cultures and ii) changes the drug could cause on the ma...

ba0005cabs.oc2.2 | Oral Communications | ECTS2016

Integrin α5 is an independent prognosis factor and a potential therapeutic target for breast cancer bone metastasis

Pantano Francesco , Croset Martine , Driouch Keltouma , Bonnelye Edith , Bednarz-Knoll Natalia , Hong Saw-See , Iuliani Michele , Fioramonti Marco , Santini Daniele , Tonini Giuseppe , Pantel Klaus , Clezardin Philippe

Aims: Using an extensive bioinformatic approach we identified integrin α5 subunit as a novel potential target to treat bone dissemination from breast cancer. Aim of this study is to confirm the value of this target.Methods: Integrin α5 mRNA expression levels were quantified by qRT-PCR, using radically resected primary tumors of 427 breast cancer patients. α5 expression at protein level by IHC on primary tumor was correlated, in an addition...

ba0005p123 | Cancer and bone: basic, translational and clinical | ECTS2016

The SRC kinase inhibitor saracatinib limits the development of osteolytic bone disease in multiple myeloma

Heusschen Roy , Muller Josephine , Binsfeld Marilene , Plougonven Erwan , Mahli Nadia , Carmeliet Geert , Leonard Angelique , Cohen-Solal Martine , Vanderkerken Karin , Beguin Yves , Menu Eline , Caers Jo

Destructive bone lesions due to osteolytic bone disease (OBD) are a major cause of morbidity and mortality in multiple myeloma (MM) patients and the development of new therapeutic strategies is of great interest. In this study, we assessed the effect of SRC inhibition with saracatinib (AZD0530, AstraZeneca) on the development of MM and its associated OBD. We first determined SRC family kinase expression in the MM microenvironment and found that myeloma cells express SRC at low...