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, 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.
Moore
R E
RE
Department of Cancer Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285.
Smith
C K
CK
Bailey
C S
CS
Voelkel
E F
EF
Tashjian
A H
AH
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001862:Bone Resorption / Q000139:chemically induced*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009638:Norepinephrine / Q000494:pharmacology; D016376:Oligonucleotides, Antisense; D009924:Organ Culture Techniques; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000318:Adrenergic beta-Agonists; D018076:DNA, Complementary; D016376:Oligonucleotides, Antisense; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D009638:Norepinephrine