Bone Abstracts

Tumor development occurs often by over-activation of members of the RAS-oncogene family (small GTPases (sGTPs)). By blocking the mevalonate pathway, aminobisphosphonates (BPs), and statines prevent activation of GTPs by inhibiting their post-translational prenylation. As we have shown, this induces apoptosis in U2OS osteosarcoma cells by re-activation of FAS expression via epigenetic DNA demethylation (1).The histone demethylase JHD...

Few drugs generate bone-stimulatory effects via epigenetic mechanisms. Modulation of CpG-residues hydroxymethylation in gene-promoters of key osteoblast-related factors (e.g., DLX5) induces their expression and increases osteoblast differentiation in vitro. The chemical properties of sulforaphane (SFN), a natural compound abundantly present in cruciferous vegetables like broccoli, suggest that it may have similar molecular and biological effects. Previous stu...

Objectives: Hypophosphatasia (HPP) is a rare hereditary disease, leading to deficits in bone and tooth mineralization, muscular as well as neurological abnormalities due to decreased enzymatic activity of the tissue-nonspecific alkaline phosphatase (TNAP, encoded by the alpl gene). In this project, the zebrafish (Danio rerio) will be established as a new and valuable animal model for HPP research. Consequently, endogenous TNAP expression should be analyzed in different zebrafi...

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Introduction: Wnt/β-catenin signalling and mechanical loading are able to inhibit adipogenesis and to stimulate osteoblastogenesis of mesenchymal stem cells1,2. The involvement of β-catenin signalling in mechanically induced bone formation has already been shown in vivo using a tibia loading model3. The aim of this study was to investigate the influence of the activation of β-catenin on the osteogenic and adip...

Background: Hypophosphatasia (HPP) is a heterogeneous rare, inherited disorder of bone and mineral metabolism caused by different mutations in the ALPL gene encoding the isoenzyme, tissue-nonspecific alkaline phosphatase (TNAP). Prognosis is very poor in severe perinatal forms with most patients dying from pulmonary complications of their skeletal disease. TNAP, a ubiquitous enzyme, is mostly known for its role in bone mineralization. TNAP deficiency, however, may als...

Dysfunctions of Wnt/β-catenin and estrogen receptor signalling resulted in impaired mechanotransduction and bone loss as in osteoporosis. Previous studies demonstrated the interaction of these pathways in mechanotransduction in vitro and in vivo. In this study, the influence of the activation of estrogen receptor and β-catenin signalling on mechanically induced bone formation was investigated in ovariectomized mice. 12-week-old mice were ovariectomi...

Osteoporosis is generally accompanied by the fatty degeneration of the bone marrow. The enhanced deposition of adipocytes may result from adipogenic differentiation of bone-marrow mesenchymal stem cells (MSC) and from the adipogenic conversion of osteoblastic cells respectively. Thus, whether this clinical observation is a cause of the disease or rather a reaction of the afflicted bone marrow remains to be elucidated.Previous microarray and bioinformatic...

Mutations of the ALPL-gene are closely related to hypophosphatasia (HPP), an inherited disorder of bone and mineral metabolism with clinically heterogeneous symptoms. To date 278 different mutations have been described, leading to reduction or completely loss of enzymatic activity of the tissue nonspecific alkaline phosphatase (TNAP).We present the case of a 6-year-old boy with clinical features and laboratory results consistent with infantile H...

Hypophosphatasia (HPP) is a rare disease characterized by low enzymatic activity of tissue-nonspecific alkaline phosphatase (TNSALP) resulting in an accumulation of its endogenous substrates like pyridoxal phosphate (PLP) and inorganic pyrophosphate (PPi). The ectoenzyme plays an important role during bone mineralization and might contribute to proper function of kidney and muscle. Neurological symptoms of HPP like seizures, anxiety disorders and depression provide ...