Bone Abstracts

Receptor activity modifying proteins (RAMPs 1, 2 and 3) are a class of important accessory proteins that interact and regulate several G-protein coupled receptor (GPCR) activity by finely modulating ligand interaction and in some cases trafficking receptors to cell surface.Predominant roles of RAMPs include ligand selectivity in receptors for Calcitonin (CT) family of peptides that comprise calcitonin, calcitonin gene related peptide, amylin and Adrenome...

Fractures in children are common; prospective cohort studies suggest narrower bones predispose to fracture. Early life events can influence later growth and development. Observational studies suggest children born to mothers with lower vitamin D levels during pregnancy have narrower bones. We investigated the effects of maternal vitamin D deficiency on offspring’s bones’ response to mechanical loading in a model system.C57BL/6 female mice (...

To use HRpQCT to investigate the effects of short term but intense exercise on the bone architecture of the distal radius in exercise-naïve women, with the ultimate aim of developing exercise regimes for children that will maximise their peak bone mass.We have recruited 16 of 20 proposed exercise-naïve women, aged 18–25, for a 12-week exercise study. The exercise consists of supervised hammering of a metal plate, using their dominant arm, ...

Adaptive responses of the skeleton to loading changes architecture and physical properties in order to optimise strength for function. However, bone is subjected to many local and circulating osteotropic factors, most acting on G-protein coupled receptors. Receptor activity modifying protein-3 is a single trans-membrane domain receptor accessory protein, which aids in trafficking of calcitonin and calcitonin-like receptors to the cell surface and changes ligand selectivity. As...

Fractures in infancy raise the spectre of child abuse; it has been suggested that lack of vitamin D could result in bone abnormalities that could predispose to fractures. We utilised a mouse model system to investigate whether vitamin D deficiency in utero alters early bone growth and development.C57BL/6 female mice received vitamin D deficient or replete diet for 6 weeks, then mated and continued on their respective diets until weaning. Pups were culled...

Objectives: Maternal vitamin D status in pregnancy is associated with neonatal bone mass, and altered DNA methylation. Mice exposed to early life vitamin D deficiency have lower bone mass and reduced bone accrual in response to mechanical loading. Using tibias from these mice we assessed DNA methylation of promoters of genetic loci important for bone growth and development.Methods: C57/BL6 mice received a vitamin D replete or deplete diet for 6 weeks per...

Despite its importance, the resorptive surface of osteoclasts has not been directly visualised. We exploited a novel approach that enables us to inspect the substrate-apposed surface of cells. To achieve this, we incubated osteoclasts on vitronectin-coated nail varnish and, afterwards, we dissolved the substrate and visualised the cells resorbing-side up in the scanning electron microscope (SEM). We then employed confocal microscopy to correlate the SEM appearances with the di...

Extracellular nucleotides, signalling through P2 receptors, play a significant role in bone biology. ATP and ADP act via the P2Y1 or P2Y12 receptors to promote osteoclast formation and activity. Bone cells express the P2Y2 receptor and, in osteoblasts, it plays a role in regulating bone mineralisation. This investigation examined the role of the P2Y2 receptor in osteoclasts. Primary osteoclasts were isolated from the bone ma...

Bisphosphonates are widely used drugs in the fight against osteoclast-mediated bone loss, including osteoporosis and Paget’s disease of bone. The first generation of these potent drugs such as clodronate, a non nitrogen-containing bisphosphonate, has been shown to inhibit osteoclast formation and osteoclastic bone resorption both in vitro and in vivo as well as inducing apoptotic cell death. Recent interest has centred on the effects of more potent nitro...

Background: Osteogenesis imperfecta (OI), the commonest inherited bone fragility disorder, affects 1/15,000 live births resulting in frequent fractures and reduced mobility, with significant impact on quality of life. Early diagnosis is important, as therapeutic advances can lead to improved clinical outcomes.Methodology and results: Trio whole exome sequencing in patients with OI identified, in two patients, compound heterozygous mutations in NBAS</...