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Curr Opin Pharmacol. 2016 Jun;28:57-68. doi: 10.1016/j.coph.2016.03.003. Epub 2016 Apr 7.

Pyrophosphate: a key inhibitor of mineralisation.

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Department of Comparative Biomedical Sciences, Royal Veterinary College, London, UK. Electronic address:
Department of Cell and Developmental Biology, University College London, London, UK.
The Botnar Research Centre, Nuffield Orthopaedic Centre, Oxford, UK; The Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK.


Inorganic pyrophosphate has long been known as a by-product of many intracellular biosynthetic reactions, and was first identified as a key endogenous inhibitor of biomineralisation in the 1960s. The major source of pyrophosphate appears to be extracellular ATP, which is released from cells in a controlled manner. Once released, ATP can be rapidly hydrolysed by ecto-nucleotide pyrophosphatase/phosphodiesterases to produce pyrophosphate. The main action of pyrophosphate is to directly inhibit hydroxyapatite formation thereby acting as a physiological 'water-softener'. Evidence suggests pyrophosphate may also act as a signalling molecule to influence gene expression and regulate its own production and breakdown. This review will summarise our current understanding of pyrophosphate metabolism and how it regulates bone mineralisation and prevents harmful soft tissue calcification.

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