Searchable abstracts of presentations at key conferences on calcified tissues

ba0003oc3.2 | Osteoclasts, gastric hormones and HIF | ECTS2014

Activation of the P2Y2 receptor enhances osteoclast function by stimulating the release of ATP, a pro-resorptive extracellular nucleotide

Orriss Isabel , Hajjawi Mark , Arnett Timothy

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...

ba0005p205 | Cell biology: osteoclasts and bone resorption | ECTS2016

Better understanding the potency and cytotoxicity of different bisphosphonates on murine osteoclast formation and activity: implications for its better clinical use in treatment cancers

Razai Mohammad , Orriss Isabel , Arnett Timothy

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...

ba0001oc6.4 | Mineralisation and energy metabolism | ECTS2013

Inhibition of PTH-induced vasorelaxation modulates its anabolic action

Gohin Stephanie , Chenu Chantal , Pitsillides Andrew , Arnett Timothy , Marenzana Massimo

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...

ba0001pp212 | Cell biology: osteoblasts and bone formation | ECTS2013

Bone-forming cultures of rat and mouse calvarial osteoblasts: key differences in protocols

Orriss Isabel , Hajjawi Mark , Huesa Carmen , MacRae Vicky , Arnett Timothy

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...

ba0001pp440 | Osteoporosis: treatment | ECTS2013

Strontium potently inhibits mineralisation in bone-forming osteoblast cultures while osteoclast formation from marrow mononuclear cells is moderately reduced

Wornham Daniel , Hajjawi Mark , Orriss Isabel , Arnett Timothy

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. ...

ba0003pp120 | Cell biology: osteoblasts and bone formation | ECTS2014

Treatment with allopurinol and oxypurinol promotes osteoblast differentiation and increases bone formation

Orriss Isabel , Arnett Timothy , George Jacob , Witham Miles

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...

ba0001oc6.1 | Mineralisation and energy metabolism | ECTS2013

Npp1 is a key regulator of skeletal and soft tissue mineralisation

Hajjawi Mark , MacRae Vicky , Huesa Carmen , Millan Jose Luis , Poulet Blandine , Arnett Timothy , Orriss Isabel

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−/...

ba0001pp234 | Cell biology: osteoclasts and bone resorption | ECTS2013

Do ecto-nucleotidases play a role in the regulation of osteoclast function?

Hajjawi Mark , MacRae Vicky , Huesa Carmen , Millan Jose Luis , Arnett Timothy , Orriss Isabel

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...

ba0005p432 | Other diseases of bone and mineral metabolism | ECTS2016

Differing mechanisms of mineralisation in vascular smooth muscle cells and osteoblasts

Patel Jessal , Zhu Dongxing , Wheeler-Jones Caroline , Arnett Timothy , MacRae Vicky , Orriss Isabel

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...