Effects of transforming growth factor-α on parathyroid hormone- and parathyroid hormone-related protein- mediated bone resorption and adenylate cyclase stimulation in vitro

Abstract

The effects of transforming growth factor-α (TGFα) were determined on the ability of parathyroid hormone (PTH) or parathyroid hormone-related protein (PTHrP) to stimulate bone resorption and adenylate cyclase in vitro. Bovine PTH-(1–34) and human PTHrP-(1–34) were equipotent in their ability to stimulate bone resorption in neonatal mouse calvaria with maximal stimulation (2.9 and 2.8-fold increases in 45Ca release, respectively) at a concentration of 10 nM. Combinations of TGFα with bPTH-(1–34) or hPTHrP-(1–34) had additive effects on their ability to stimulate bone resorption when submaximal concentrations of the agonists were used. There was no evidence of synergism between TGFα and bPTH-(1–34) or hPTHrP-(1–34) in their ability to stimulate bone resorption in vitro, nor was TGFα able to increase bone resorption induced by maximal concentrations of bPTH-(1–34) or hPTHrP-(1–34). TGFα potentiated the effects of either bPTH-(1–34) or hPTHrP-(1–34) on the stimulation of adenylate cyclase in osteoblast-like ROS 17 2.8 cells. These data indicate that TGFα has additive effects with submaximal concentrations of PTH or PTHrP on their ability to stimulate bone resorption which may be important in the pathogenesis of humoral hypercalcemia of malignancy.