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...

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...

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...

Kit ligand/c-Kit receptor tyrosine kinase complex has been implicated as a target for bone remodeling process. Loss of function mutation in c-Kit causes low bone mass in KitW/W-v (W/Wv) mice. However, these mice are sterile and it is unclear whether the observed skeletal phenotype is secondary to sex hormone deficiency. To address this question, the skeletal phenotype of KitW...

Inflammatory processes play a role in osteoclastogenesis. C-reactive protein (CRP), an acute phase reactant that reflects different degree of inflammation. More recently, accumulating evidence suggest that CRP is not only an inflammatory marker but also direct cause of diseases. Therefore, we examined the direct effects of CRP on osteoclast formation using RAW 264.7 cells. CRP significantly inhibited RANKL-induced TRAP-positive multinucleated cell formation in RAW 264.7 cell c...

Biographical DetailsAmaka C Offiah is Senior Lecturer and Consultant Paediatric Radiologist at the University of Sheffield and Sheffield Children’s Hospital. She has a specialist interest in the musculoskeletal system. She has co-authored two books, seven book chapters, published 67 peer-reviewed articles and given over 100 invited national and international lectures. She is Convenor...

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 ...

We have previously shown a high prevalence of vitamin D inadequacy (serum 25-hydroxyvitamin D (S25(OH)D) <50 nmol/l) in adolescents (14–18 years) in the UK (51°N)(1). It is well recognised that vitamin D deficiency (S25(OH)D <25 nmol/l) increases the risk of rickets and impaired growth in adolescents, however the optimal vitamin D status for bone health is debated. The aim of this study was to investigate the effects of vitamin D status on bone hea...

Suppression of parathyroid hormone (PTH) has been suggested as a potential biochemical outcome measure for determining the optimal serum 25-hydroxyvitamin D (S25(OH)D) concentration for bone health in adults. However, in adolescents increases in PTH may not be driven by the same mechanisms and may not be detrimental to bone health. Adolescent studies have provided a wide range of estimates of the S25(OH)D concentration at which PTH plateaus (40–90 nmol/l), with some repor...