CHARACTERIZATION OF BETA-ADRENERGIC RECEPTORS ON RAT AND HUMAN OSTEOBLAST-LIKE CELLS AND DEMONSTRATION THAT BETA-RECEPTOR AGONISTS CAN STIMULATE BONE-RESORPTION IN ORGAN-CULTURE

We have shown by receptor-binding analyses that the beta-2 adrenergic receptor is present on rat ROS 17/2.8 osteoblast-like cells. This was confirmed by PCR amplification of cDNA copied from the mRNA. The beta- 1 adrenoreceptor subtype was absent and its mRNA was not detectable, e ven at the level of sensitivity afforded by PCR analysis. The beta-adr energic receptors present on ROS 17/2.8 cells were functional as measu red by ligand-induced enhancement of cAMP production. We investigated whether adrenergic agonists could mimic the action of PTH to stimulate bone resorption in neonatal mouse calvariae in organ culture. PTH ind uced a large increase in cAMP while norepinephrine and isoproterenol i nduced a small but significant increase. In the presence of a phosphod iesterase inhibitor and an antioxidant, norepinephrine consistently st imulated bone resorption. In order to determine whether functional bet a-adrenergic receptors were unique to ROS 17/2.8 cells, human SaOS-2 o steoblast-like cells were also examined for enhancement of cAMP produc tion by norepinephrine, and essentially the same results were obtained . Thus, adrenergic agonists efficiently activate beta-receptors on two osteoblast-like cells and can stimulate bone resorption in intact mou se calvariae.