Extracellular pyrophosphate: The body's "water softener".

Orriss, Isabel R · Bone · 2020

review · Level V

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Abstract

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

Medical subject headings