Type II Na+-P-i cotransporters in osteoblast mineral formation: Regulation by inorganic phosphate

During calcification of bone, large amounts of phosphate ( P-i) must be transported from the circulation to the osteoid. Likely candidates for osteoblast P-i transport are the type II sodium-phosphate cotransporters NaPi- IIa and NaPi-IIb that facilitate transcellular P-i flux in kidney and intestine, respectively. We have therefore determined the cotransporters' expression in osteoblast- like cells. We have also studied the cotransporters' regulation by P-i and during mineralization in vitro. Phosphate uptake and cotransporter protein expression was investigated at early, late and mineralizing culture stages of mouse ( MC3T3-E1) and rat ( UMR- 106) osteoblast- like cells. Both NaPi- IIa and NaPi- IIb were expressed by both osteoblast- like cell lines. NaPi- IIa was upregulated in both cell lines one week after confluency. After 7 days in 3mM P-i NaPi- IIa was strongly upregulated in both cell lines. NaPi- IIb expression was unaffected by both culture stage and P-i supplementation. The expression of both cotransporters was unaffected by P-i deprivation. In vitro mineralization at 1.5mM P-i was preceded by a three- fold increase in osteoblast sodium- dependent P-i uptake and a corresponding upregulation of both NaPi- IIa and NaPi- IIb. Their expression thus seem regulated by phosphate in a manner consistent with their playing a role in transcellular P-i flux during mineralization. Copyright (c) 2007 S. Karger AG, Basel