Effects of beta-adrenergic blockade in an osteoblast-like cell line.
The beta-adrenergic blocking agent propranolol was shown in previous studies to increase orthotopic bone formation in rats. To understand the cellular mechanisms underlying this observation, propranolol was tested for its effects on osteoblastic cells, which possess adenylate cyclase-coupled beta-adrenergic receptors. The ability of propranolol to modulate parathyroid hormone (PTH) and isoproterenol effects on adenylate cyclase activity and on alkaline phosphatase expression was studied in the osteoblast-like rat osteosarcoma cell line ROS 17/2.8. At concentrations between 0.1 and 10 microM, DL-propranolol specifically inhibited adenylate cyclase stimulation by the beta-adrenergic agonist isoproterenol, but did not alter either basal or PTH-stimulated activity. At these concentrations, propranolol also blunted the inhibition of alkaline phosphatase activity by isoproterenol but not PTH. Propranolol alone had minimal effects on ROS alkaline phosphatase activity at low concentrations (0.1-1 microM), but became inhibitory at high concentrations (10-100 microM). Thus, the direct effects of physiologically relevant propranolol concentrations on osteoblastic cells can be attributed principally to beta-adrenergic blockade. These findings further suggest that propranolol may enhance bone formation by preserving osteoblastic activity in the face of inhibition by beta-adrenergic agonists.
Department of Orthopaedics, Mount Sinai School of Medicine, New York, NY 10029-6574.
R J
RJ
Majeska
B
B
Minkowitz
W
W
Bastian
T A
TA
Einhorn
D000262:Adenylyl Cyclases / Q000378:metabolism / Q000502:physiology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001859:Bone Neoplasms / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D007545:Isoproterenol / Q000494:pharmacology; D012516:Osteosarcoma / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D010281:Parathyroid Hormone / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology / Q000473:pathology
D000319:Adrenergic beta-Antagonists; D010281:Parathyroid Hormone; D011433:Propranolol; D000469:Alkaline Phosphatase; D000262:Adenylyl Cyclases; D007545:Isoproterenol