Searchable abstracts of presentations at key conferences on calcified tissues

ba0003oc1.4 | Phosphate metabolism, fracture repair and osteoarthritis | ECTS2014

Long-term Fgf23 deficiency induces renal and skeletal PTH resistance in vitamin D receptor-ablated mice

Andrukhova Olena , Murali Sathish Kumar , Zeitz Ute , Erben Reinhold G.

Fibroblast growth factor-23 (FGF23) is a hormone originating from osteocytes with suppressive actions on renal phosphate reabsorption and vitamin D synthesis. We recently identified FGF23 as a calcium-conserving hormone, regulating the membrane transport of the epithelial calcium channel TRPV5 in distal renal tubules. Here, we analyzed the long term sequelae of Fgf23 deficiency and renal calcium wasting on bone and mineral metabolism in 9-month-old mice lacking both Fgf23<...

ba0005p90 | Calciotropic and phosphotropic hormones and mineral metabolism | ECTS2016

Bone loss in KLHL3 knock-in mice characterized by a pseudohypoaldosteronism type II-like phenotype is mediated by renal PTH resistance

Andrukhova Olena , Zhang Jinwei , Alessi Dario , Erben Reinhold

Pseudohypoaldosteronism type II (PHAII) is a hereditary disease characterized by hypertension, hypercalciuria and osteopenia. PHAII is caused by mutations in with-no-lysine kinase 1 (WNK1), WNK4, or the cullin RING ligase family members kelch-like 3 (KLHL3) or cullin 3 (CUL3). All mutations result in up-regulation of the WNK signalling pathway which activates thiazide-sensitive Na-Cl cotransporters (NCC) in renal distal tubules, leading to salt retention and hypertension in PH...

ba0003oc1.3 | Phosphate metabolism, fracture repair and osteoarthritis | ECTS2014

Klotho deficiency impairs mineralization by vitamin D hormone-driven upregulation of osteopontin and pyrophosphate in bone

Murali Sathish Kumar , Roschger Paul , Zeitz Ute , Klaushofer Klaus , Andrukhova Olena , Erben Reinhold G.

Lack of Klotho, the co-receptor for the bone-derived hormone fibroblast growth factor-23 (FGF23), leads to a severe impairment in bone mineralization in mice. However, the mechanisms underlying the Klotho deficiency-associated defects in bone mineralization are still poorly understood. Here, we sought to elucidate the vitamin D independent role of Klotho in bone mineralization. To ablate increased vitamin D signaling in Klotho knockout mice (Kl−/−), we c...

ba0003pp107 | Cell biology: osteoblasts and bone formation | ECTS2014

Osteoblast-specific overexpression of amphiregulin leads to transient increase in cancellous bone mass in mice

Vaidya Mithila , Lehner Diana , Handschuh Stephan , Jay Freya , Schneider Marlon R , Erben Reinhold G

It is well known that the epidermal growth factor receptor (EGFR), its ligands, and the structurally related receptor ERBB2/neu are expressed in skeletal cells. However, the functions of EGFR ligands in bone cells remain poorly defined. In this study, we employed a transgenic mouse line overexpressing the EGFR ligand amphiregulin (AREG) specifically in osteoblasts under the α1(I)-collagen promoter. AREG-tg mice did not show changes in body weight or gross phenotype. Compa...

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 ...

ba0007p169 | (1) | ICCBH2019

Rescue diet restores bone matrix mineralization in mice with a non-functioning vitamin D receptor

Misof Barbara , Blouin Stephane , Hartmann Markus , Hofstaetter Jochen , Klaushofer Klaus , Zwerina Jochen , Roschger Paul , Erben Reinhold

Objectives: Mice with a non-functioning vitamin D receptor (VDR mutants) develop severe secondary hyperparathyroidism, which can be rescued by a diet enriched with calcium, phosphate and lactose. In this work, we studied the effects of a low calcium challenge (CD), normal calcium (ND) and a calcium enriched rescue diet (RD) on the bone mineralization density distribution (BMDD) and osteocyte lacunae sections (OLS) in these mice.Methods: BMDD and OLS were...