Extracellular pyrophosphate: The body's "water softener"

Extracellular pyrophosphate (ePP_i) was first identified as a key endogenous inhibitor of mineralisation in the 1960's by Fleisch and colleagues. The main source of ePP_i 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 ePP_i. The major function of ePP_i 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 ePP_i can influence gene expression and regulate its own production and breakdown. This review will summarise our current knowledge of ePP_i metabolism and how it acts to prevent pathological soft tissue calcification and regulate physiological bone mineralisation.