Human parathyroid hormone carboxyterminal peptide (53-84) stimulates alkaline phosphatase activity in dexamethasone-treated rat osteosarcoma cells in vitro.
Previous studies in our laboratory have demonstrated relatively large numbers of cell surface binding sites for the carboxylterminal (53-84) region of PTH on ROS 17/2.8 rat osteosarcoma cells, a clonal osteoblast-like cell line. In order to gain insight into the significance of these carboxylterminal binding sites, we studied the effect of intact bovine PTH (1-84), its aminoterminal fragment bovine PTH (1-34), and the human PTH carboxylterminal fragment (53-84) on alkaline phosphatase activity in dexamethasone-treated rat osteosarcoma (ROS) 17/2.8 cells. While bovine PTH (1-84) and its aminoterminal 1-34 fragment inhibited alkaline phosphatase activity, we saw a dose-related stimulation of activity by human PTH (53-84), with maximal stimulation occurring after 120 hours, at a concentration of 10(-8) M. The effect was not seen in dexamethasone-untreated cells. To our knowledge, this is the first published demonstration of biological activity of this carboxylterminal PTH peptide, previously thought to be inactive. It is likely that dexamethasone caused differentiation of cells to a type more sensitive to human PTH (53-84). Further studies are necessary to elucidate the physiological significance of these findings.
Murray
T M
TM
Division of Endocrinology and Metabolism, St. Michael's Hospital, Toronto, Ontario, Canada.
Rao
L G
LG
Muzaffar
S A
SA
Ly
H
H
D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D012516:Osteosarcoma / Q000201:enzymology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats
D010281:Parathyroid Hormone; D010446:Peptide Fragments; C035453:parathyroid hormone (53-84); D003907:Dexamethasone; D000469:Alkaline Phosphatase