Skeletal mineralisation is a process of fundamental importance to all vertebrate animal species. During skeletal growth and remodelling, calcium and phosphate (Pi) are required for the formation of biological apatites. The rate at which mineralisation occurs is dependent, in part, on the local availability of Pi and calcium. Although implication of Pi transporters in mineralisation process appears evident, the identity of this (or these) protein(s) is yet to be determined. In vertebrae, the type III cotransporters (PiT1 and PiT2) are the only NaPi cotransporters identified so far in skeletal tissues, and are thus considered as essential suppliers of Pi for skeletal mineralisation, despite the absence of in vivo evidence. This putative role in bone mineralisation was also derived from in vitro studies that have showed that PiT1, but not PiT2, expression is regulated by factors regulating bone cells. However, we recently demonstrated that PiT1 hypomorphic adult mice have a normal bone mineralisation. To assess the role of PiT2 in bone development, growth and mineralisation, we underwent the phenotypic characterisation of PiT2 knockout mice (french ethical approval #02286.01). We show that PiT2-/- mice are subviable and that 50% of the PiT2-/-mice are dying off around birth. After birth, we observe that PiT2-/- mice are growth retarded and exhibit impaired skeletal mineralisation. Quantitative faxitron analyses show lower bone mineral content and weaker and less stiff bones in PiT2-/- mice compared with controls. Analyses of histological sections of the upper tibia from PiT2-/- mice show a decreased bone formation and also a reduced growth-plate mineralisation at postnatal day 16. We are now investigating expression of key regulators of Pi homeostasis. To this aim, we are performing conventional biochemical analyses and RT-qPCR from bone, kidney, gut and blood samples. Altogether, these data suggest that PiT2 is a key sodium-phosphate cotransporter for skeletal mineralisation.
Disclosure: The authors declared no competing interests.