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

Bone Miner. 1993 Dec;23(3):301-15. doi: 10.1016/s0169-6009(08)80105-5.

Abstract

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, even at the level of sensitivity afforded by PCR analysis. The beta-adrenergic receptors present on ROS 17/2.8 cells were functional as measured 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 induced a large increase in cAMP while norepinephrine and isoproterenol induced a small but significant increase. In the presence of a phosphodiesterase inhibitor and an antioxidant, norepinephrine consistently stimulated bone resorption. In order to determine whether functional beta-adrenergic receptors were unique to ROS 17/2.8 cells, human SaOS-2 osteoblast-like cells were also examined for enhancement of cAMP production 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 mouse calvariae.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • Base Sequence
  • Binding Sites
  • Bone Resorption / chemically induced*
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism
  • Cyclic AMP / metabolism
  • DNA, Complementary / metabolism
  • Humans
  • Mice
  • Molecular Sequence Data
  • Norepinephrine / pharmacology
  • Oligonucleotides, Antisense
  • Organ Culture Techniques
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Phosphodiesterase Inhibitors / pharmacology
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, Adrenergic, beta / metabolism*
  • Tumor Cells, Cultured

Substances

  • Adrenergic beta-Agonists
  • DNA, Complementary
  • Oligonucleotides, Antisense
  • Phosphodiesterase Inhibitors
  • RNA, Messenger
  • Receptors, Adrenergic, beta
  • Cyclic AMP
  • Norepinephrine