TRANSFORMING GROWTH FACTOR-BETA(1) REGULATES STEADY-STATE PTH PTHRP RECEPTOR MESSENGER-RNA LEVELS AND PTHRP BINDING IN ROS-17/2.8 OSTEOSARCOMA CELLS/

The effect of transforming growth factor beta(1) (TGF-P,) on the expre ssion of mRNA for the parathyroid hormone receptor and binding of iodi nated parathyroid hormone-related protein in ROS 17/2.8 osteosarcoma c ells was evaluated. TGF-beta(1) stimulated a 2-7-fold increase in stea dy state mRNA levels for the parathyroid hormone receptor at a maximal dose of 5 ng/ml, with increased levels of expression at 6 h of TGF-be ta(1)-incubation, and peak levels at 8-24 h. Receptor binding studies revealed a significant increase in PTHrP-specific binding with TGF-bet a(1) doses as low as 0.5 ng/ml and a 55% increase in numbers of recept ors with no alteration in binding affinity with 5.0 ng/ml TGF-beta(1). Time course studies indicated that receptor binding was increased at 24 h with peak levels reached at 48 h of treatment. PTH-stimulated cAM P levels were significantly increased in ROS 17/2.8 cells treated with TGF-P, (0.5 ng/ml) for 48 h. These data indicate that TGF-beta(1) upr egulates steady-state mRNA, ligand binding and PTH/PTHrP receptor sign aling in rat osteosarcoma cells. The effects of TGF-beta(1) on bone ma y be attributed in part to regulation of the PTH/PTHrP receptor at the molecular level.