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Extracellular pyrophosphate: The body's “water softener”

Orriss, I R


I R Orriss


Extracellular pyrophosphate (ePPi) was first identified as a key endogenous inhibitor of mineralisation in the 1960's by Fleisch and colleagues. The main source of ePPi seems to be extracellular ATP which is continually released from cells in a controlled way. ATP is rapidly broken down by enzymes including ecto-nucleotide pyrophosphatase/phosphodiesterases to produce ePPi. The major function of ePPi is to directly inhibit hydroxyapatite formation and growth meaning that this simple molecule acts as the body's own “water softener”. However, studies have also shown that ePPi can influence gene expression and regulate its own production and breakdown. This review will summarise our current knowledge of ePPi metabolism and how it acts to prevent pathological soft tissue calcification and regulate physiological bone mineralisation.


Orriss, I. R. (2020). Extracellular pyrophosphate: The body's “water softener”. BONE,

Journal Article Type Review
Acceptance Date Jan 16, 2020
Publication Date Jan 16, 2020
Deposit Date Jan 21, 2020
Publicly Available Date Jan 17, 2021
Journal BONE
Print ISSN 8756-3282
Publisher Elsevier
Peer Reviewed Peer Reviewed
Public URL


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