EXPRESSION OF A NEWLY IDENTIFIED PHOSPHATE TRANSPORTER RETROVIRUS RECEPTOR IN HUMAN SAOS-8 OSTEOBLAST-LIKE CELLS AND ITS REGULATION BY INSULIN-LIKE-GROWTH-FACTOR-I

The cell surface receptor for gibbon ape leukemia virus (Glvr-1) was r ecently demonstrated to serve normal cellular functions as a sodium-de pendent phosphate (NaPi) transporter. This protein belongs to a newly identified phosphate transporter/retrovirus receptor gene family disti nct from renal type I and II NaPi transporters. Although inorganic pho sphate (Pi) transport is an important function of osteoblasts and of t he matrix vesicles produced by these cells in the context of bone matr ix calcification, the molecular identity of the NaPi transport system( s) present in this cell type is still unknown. In contrast to Pi uptak e mediated by renal NaPi transporters, the activities of both the oste oblastic transport system and Glvr-1 are decreased at alkaline pH, and this observation led us to investigate expression of this transporter in human SaOS-2 osteosarcoma cells. Northern blotting analysis reveal ed the presence of a 4-kilobase Glvr-1 transcript. The expression of G lvr-1 messenger RNA (mRNA) was increased in response to insulin-like g rowth factor I (IGF-I). Associated with this effect, a selective, dose -and time-dependent stimulation of NaPi transport was observed. Actino mycin D and cycloheximide abolished the increase in NaPi transport, wh ich thus appeared to be dependent on RNA and protein synthesis. The in crease in Glvr-1 mRNA induced by IGF-I was dose dependent and transien t, peaking after 4 h (similar to 4-fold increase in response to 10(-7) M IGF-I). It preceded the maximal expression of NaPi transport stimul ation (173-235% of control), which was observed after 18-24 h. Inducti on of Glvr-1 mRNA expression by IGF-I was inhibited by actinomycin D, suggesting that this effect was related to an increase in gene transcr iption. The stability of Glvr-1 mRNA was not altered by IGF-I, and Glv r-1 mRNA induction did not require the synthesis of new proteins. Thes e data demonstrate for the first time regulated expression of mRNA enc oding the type III NaPi transporter Glvr-1 in osteoblast-like cells. T hey also suggest that this new transporter family may be involved in P i handling in osteogenic cells and in its regulation by osteotropic fa ctors.