Bone Abstracts

Tyrosine kinase c-Src plays an important role in actin ring formation and bone resorption activity in osteoclasts. Therefore, c-Src has been targeted for the treatment of osteolytic disorders. In the present study, we investigated anti-resorptive effect of dibenzazepine (DBZ), one of the γ-secretase inhibitors (GSIs), on osteoclast-mediated excessive bone resorption. DBZ did not affect osteoclast differentiation, but disturbed actin ring formation and inhibited osteoclast...

Distal-less homeobox 5 (Dlx5) is a transcription factor that enhances osteogenic differentiation of mesenchymal stem cells via upregulating the expression of Runx2 and other osteoblast phenotypic genes. We have previously demonstrated that Dlx5 also downregulates adipogenic differentiation of mesenchymal stem cells and that insulin decreases expression levels of Dlx5 via increasing expression levels of miR-124, a microRNA targeting 3′UTR of Dlx5. However, the mechanism o...

Objectives: Osteonecrosis (ON) and decline of bone mineral density (BMD) are serious side effects during and after treatment of childhood acute lymphoblastic leukemia (ALL). It is unknown whether ON and low BMD co-occur in the same patients, and whether these two osteogenic side-effects can mutually influence each other’s development.Methods: BMD and the incidence of symptomatic ON were prospectively assessed in a national cohort of 466 patients wit...

Prostate cancer is the most prevalent cancer in men and metastatic spread to bone is detected in up to 80% of patients with advanced disease at autopsy. PCa can progress from treatable androgen-dependent stage to castration-resistant stage with distant metastases for which novel therapeutic targets and strategies are urgently needed. Here we identify the cell surface/secreted oncoprotein Cripto as a potential target for the diagnosis and treatment of metastatic prostate cancer...

Background: Pseudohypoparathyroidism (PHP) is a group of heterogeneous endocrine disorders characterised by hormone resistance, primarily to parathyroid hormone (PTH). The resistance is caused by defects in the GNAS gene, which encodes the Gsα protein that activates the cAMP pathway. PHP patients demonstrate elevated plasma PTH, hypocalcaemia, hyperphosphataemia with normal renal function. PTH resistance can be confirmed by Ellsworth-Howard test (PTH s...

: This study analyses the long-term effect of rhGH on final height (FH) and bone health in renal transplanted patients.Twenty-one young adult patients, aged 17–26 years, were studied. Group A consisted of 15 patients (12 boys) who received rhGH during 3.0 years before transplantation. After transplantation three boys needed rhGH again for 3.5 years. In group B six patients (three boys) didn’t need rhGH before transplantation, three girls receiv...

Bone density (BMD) loss is a consequence of aromatase inhibitors (AI) treatment of breast cancer. B-ABLE cohort includes 391 postmenopausal women with early breast cancer starting AI therapy. Participants experienced a 1.98% (95% CI 1.54–2.42% P<0.0001) bone loss at lumbar spine (LS) and 1.24% (95% CI 0.81–1.67% P<0.0001) bone loss at femoral neck (FN) after 1 year on AI therapy and a 3.51% (95% CI 3.00–4.03% P<0.0001) bone...

High Bone Mass (HBM) osteogenesis imperfecta (OI) is caused by dominant mutations in the C-propeptide cleavage site of COL1A1 or COL1A2, characterized by bone hypermineralization. To elucidate the role of C-propeptide processing in bone mineralization and development, we generated heterozygous HBM mice with both residues (Ala-Asp) of the COL1A1 cleavage site substituted (Thr-Asn) to prevent processing by BMP1. Two, 6- and 12-month WT and HBM bones were examin...

Familial expansile osteolysis (FEO) is characterised by focal areas of increased bone turnover driven by bone-resorbing osteoclasts. The syndrome is caused by a heterozygous tandem insertion duplication mutation within the signal peptide region of TNFRSF11a (encoding receptor activator of NFκB; RANK). Our recent research has demonstrated that heterotrimeric receptor formation may hold the key to the disease phenotype. We have shown previously that, whilst homozygous overe...

Osteocytes may function as mechanotransducers by regulating local osteoclastogenesis. Reduced availability of oxygen, i.e. hypoxia could occur during disuse, bone development and fracture. Receptor activator of nuclear factor-κB ligand (RANKL) is an osteoblast/stromal cell derived essential factor for osteoclastogenesis. Hypoxia induced osteoclastogenesis via increased RANKL expression in osteoblasts was demonstrated. Hypoxic regulation of gene expression general...