Cellular calcification induced by inorganic polyphosphate involves ATP depletion and opening of the mitochondrial permeability transition pore (mPTP)

Abstract

Inorganic polyphosphate (polyP) is a linear polymer containing tens to hundreds of orthophosphate residues linked by high‐energy phosphoanhydride bonds. PolyP promotes osteocalcification and bone mineralization in both mouse and human osteoblastic cells. In the present study, we examined the molecular mechanism by which polyP affects mitochondrial metabolism to promote cellular calcification in MC3T3‐E1 osteoblastic cells. The cellular content of adenosine triphosphate (ATP) was diminished one day after polyP treatment, and this was accompanied by increased conversion to adenosine diphosphate. Furthermore, mitochondrial membrane potential was significantly decreased in polyP‐treated cells. These results suggest that the depletion of intracellular ATP and the decrease in mitochondrial membrane potential induced by polyP treatment may be a trigger to promote cell calcification.

Keywords

• adenosine triphosphate
• calcification
• inorganic polyphosphate
• mitochondria
• mitochondrial permeability transition pore