Regulation of plasminogen activator production by bone-resorbing hormones in normal and malignant osteoblasts.
The plasminogen activator (PA) activity of clonal rat osteogenic sarcoma cell (phenotypically osteoblast) and of osteoblast-rich rat calvarial cells is shown to be increased by treatment with the bone-resorbing hormones, PTH, 1,25-dihydroxyvitamin D3, prostaglandin E2, and epidermal growth factor. Dose-dependent increases were observed, after a lag period of 4 to 8 h. Stimulated and control PA activities were inhibited by actinomycin D and cycloheximide but not by cytosine arabinoside. Glucocorticoid hormones prevented the hormone stimulation, but other steroids did not. Calcitonin had no effect either on basal or on hormone-treated PA activity. Isobutyl-methylxanthine alone increased PA activity and enhanced responsiveness to PTH and to prostaglandin E2. These data point to a common pathway in the actions upon osteoblasts of several hormones with diverse initial cellular actions and raise the possibility that the PA/plasmin system may contribute to cellular mechanisms of bone turnover.
Hamilton
J A
JA
Lingelbach
S
S
Partridge
N C
NC
Martin
T J
TJ
D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D002116:Calcitonin / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D015232:Dinoprostone; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D007700:Kinetics; D003012:Microbial Collagenase / Q000096:biosynthesis; D009712:Nucleotides, Cyclic / Q000502:physiology; D010006:Osteoblasts / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology; D010960:Plasminogen Activators / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000494:pharmacology; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D005938:Glucocorticoids; D009712:Nucleotides, Cyclic; D010281:Parathyroid Hormone; D011458:Prostaglandins E; D012710:Serum Albumin, Bovine; D004815:Epidermal Growth Factor; D012313:RNA; D002116:Calcitonin; D010960:Plasminogen Activators; D003012:Microbial Collagenase; D002117:Calcitriol; D015232:Dinoprostone