Stimulation by parathyroid hormone-related protein and transforming growth factor-alpha of phosphate transport in osteoblast-like cells

Abstract

Parathyroid hormone (1-34) [PTH-(1-34)] has been shown to stimulate sodium-dependent phosphate transport (NaPiT) in UMR-106 osteoblast-like cells through a cAMP-dependent mechanism. Whether a synthetic amino-terminal fragment of parathyroid hormone-related protein (PTHrP) or the full-length molecule, which are recognized to interact with the same receptor as PTH, affect NaPiT in the same way is not known. We investigated and compared the effects of bPTH-(1-34), PTHrP-(1-34), and PTHrP-(1-141) on NaPiT and cAMP production in the osteoblastic cell line UMR-106. Each of the three peptides increased cAMP production and exerted a concentration-dependent stimulation of NaPiT after incubation for 4-6 h. We also studied the effect of transforming growth factor-alpha (TGF-alpha), which is another tumoral product secreted by certain hypercalcemia-associated tumors, on NaPiT and the TGF-alpha-induced modulation of the response to PTHrP or PTH. TGF-alpha caused a 30% stimulation of NaPiT, which remained stable from 6 to 24 h, by a cAMP-independent mechanism. In contrast, TGF-alpha attenuated cAMP production stimulated by PTH, PTHrP-(1-34), or PTHrP-(1-141). PTHrP or PTH did not further increase NaPiT in TGF-alpha-treated cells. These results indicate that NaPiT, a possibly important function of osteoblastic cells, was similarly affected by PTH and PTHrP. TGF-alpha increased NaPiT and modulated in a similar way the effects of both PTH and PTHrP.