Bone Abstracts

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...

The relationship between bone formation and blood flow is unclear. Recently, PTH was reported to activate production of nitric oxide (NO), a potent vasorelaxing agent, in endothelial cells and we and others have confirmed a strong vasorelaxing action of PTH in vivo in the mouse. Here, we tested the hypothesis that a potent NO synthase inhibitor (L-NAME: NG-nitro-L-arginine methyl ester) may alter the effect of intermittent PTH (iPTH) on b...

The in vitro culture of calvarial osteoblasts from neonatal rodents remains an important method for studying the regulation of osteoblast function. Widespread use of transgenics has created a particular need for a reliable, simple method that allows the differentiation and bone-forming activity of mouse osteoblasts to be studied directly. We have established such a method and have identified key differences in optimal culture conditions between mouse and rat osteoblas...

Strontium ranelate (SrR) is now widely used for the prevention of osteoporotic fractures. The mechanisms by which this occurs, however, remain unclear. We investigated the actions of Sr2+ salts in bone-forming cultures of primary osteoblasts from rat calvariae. Osteoblasts were treated continuously with either SrR or SrCl2 for 14 days. Abundant, discretely mineralised ‘trabecular’ bone structures formed in alizarin red-stained control cultures. ...

Allopurinol and, and its active metabolite, oxypurinol are widely used in the treatment of gout and hyperuricemia. They act by inhibiting xanthine oxidase an enzyme in the purine degradation pathway that converts xanthine to uric acid. This oxygen-dependent reaction also results in the generation of superoxide free radicals. The aim of this investigation was to examine the effect of allopurinol and oxypurinol on osteoblast differentiation and function. Rat calvarial osteoblast...

Ecto-nucleotide pyrophosphatase/phosphodiesterases (NPPs) hydrolyse nucleotide triphosphates to the corresponding nucleotide monophosphate and the mineralisation inhibitor, pyrophosphate (PPi). This investigation examined the role of NPP1 in bone and soft tissue mineralisation using a mouse model lacking NPP1(Enpp1−/−). At physiological pH 7.35, cultured Enpp1−/...

Extracellular nucleotides stimulate both the formation and resorptive activity of osteoclasts. Ecto-nucleotide pyrophosphatase/phosphodiesterases (NPPs) hydrolyse extracellular nucleotide triphosphates to their corresponding monophosphate and pyrophosphate (PPi). We investigated if osteoclasts express functional NPPs and whether Enpp1 gene deletion influenced osteoclast formation and activity. Osteoclasts were formed from the bone marrow of 8 and 15 week old knockou...

Vascular calcification (VC) involves hydroxyapatite deposition in the arteries and cardiac muscle. VC is thought to share some outward similarities to skeletal mineralisation and has been associated with the transdifferentiation of vascular smooth muscle cells (VSMCs) to an osteoblast-like phenotype. We have previously shown that ATP, UTP and synthetic ATP-analogues (α, β-meATP, β, γ-meATP, Bz-ATP) (≥1 μM) act to potently inhibit both bone minera...