Cyclic AMP-mediated stabilization of osteocalcin mRNA in rat osteoblast-like cells treated with parathyroid hormone.
Osteocalcin (bone gamma-carboxyglutamic acid-containing protein) is exclusively produced by osteoblasts, which are the major target cells of parathyroid hormone (PTH) in bone. This study examined the effect of human (h) PTH(1-34) on osteocalcin gene expression in the rat osteoblast-like osteosarcoma cells ROS17/2.8. hPTH(1-34) increased in a dose-dependent manner the steady state levels of osteocalcin mRNA 2- to 3-fold with an ED50 of about 5 X 10(-10) M. This effect was detectable at 12 h, peaked at 24 h, and lasted at least up to 48 h. Forskolin, cyclic 8-bromo-AMP, isobutylmethylxanthine, cholera toxin, and (-)-isoproterenol similarly elevated osteocalcin mRNA. hPTH(1-34) did not alter the transcriptional rate of the osteocalcin gene, estimated by nuclear run-on assays, but increased the stability of osteocalcin mRNA. hPTH(1-34) also increased 2- to 3-fold the osteocalcin level in the culture media determined by radioimmunoassay. PTH, thus, promoted osteocalcin gene expression in these cells at least in part through mRNA stabilization via cyclic AMP mediation, a mechanism known only in few systems.
Noda
M
M
Department of Bone Biology and Osteoporosis Research, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
Yoon
K
K
Rodan
G A
GA
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D010006:Osteoblasts / Q000378:metabolism*; D015675:Osteocalcin; D012516:Osteosarcoma; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D019379:Teriparatide
D002135:Calcium-Binding Proteins; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D012333:RNA, Messenger; D015675:Osteocalcin; D019379:Teriparatide; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D002772:Cholera Toxin; D000242:Cyclic AMP; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine