Bone Abstracts

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<...

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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...

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...

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...

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 ...

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...