Polyphosphate (polyP) is a naturally occurring, anionic polymer comprising orthophosphate groups linked together by high-energy anhydrous phosphate bonds. In mammals, high levels of polyphosphate are found in platelets and osteoblasts, suggesting that it constitutes a source of orthophosphate and/or energy for bone mineralisation. In this issue (p. ), Werner Müller, Xiaohong Wang and colleagues use polyP nanoparticles in osteoblast-like cells to shed light on the energy basis of hydroxyapatite production during bone mineralisation. They followed a standardised protocol to produce amorphous, spherical, Ca2+-complexed polyP nanoparticles. The diameter of the nanoparticles was measured to be between 50 and 130 nm, making them of suitable size for uptake through clathrin-mediated endocytosis. Using transmission electron microscopy, the authors demonstrated that adding polyP nanoparticles increased the number of mitochondria in SaOS-2 osteoblast-like cells. In addition, polyP nanoparticles increased the translocation of the exopolyphosphatase alkaline phosphatase to the membrane – an event previously suggested to be a marker of osteoblast activation. Furthermore, polyP nanoparticles caused an increase in both intra- and extracellular ATP levels. This effect was even stronger in cells that had been pre-treated with a mineralisation-activation cocktail. Taken together, these data provide evidence to support the idea that polyP serves as metabolic fuel for hydroxyapatite formation during bone mineralisation.
