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

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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-α (TGF-α), which is another tumoral product secreted by certain hypercalcemia-associated tumors, on NaPiT and the TGF-α-induced modulation of the response to PTHrP or PTH. TGF-α caused a 30% stimulation of NaPiT, which remained stable from 6 to 24 h, by a cAMP-independent mechanism. In contrast, TGF-α attenuated cAMP production stimulated by PTH, PTHrP-(1–34), or PTHrP-(1–141). PTHrP or PTH did not further increase NaPiT in TGF-α-treated cells. These results indicate that NaPiT, a possibly important function of osteoblastic cells, was similarly affected by PTH and PTHrP. TGF-α increased NaPiT and modulated in a similar way the effects of both PTH and PTHrP.
Funding Information
  • Swiss National Science Foundation (3200-25.535)