Biochemical and morphological analysis of the interaction of epidermal growth factor and parathyroid hormone with UMR 106 osteosarcoma cells.
The interaction of epidermal growth factor (EGF) and PTH with UMR 106 osteosarcoma cells was examined biochemically and morphologically. EGF inhibited PTH-stimulated adenylate cyclase activity in association with a reduction in PTH receptors and a decrease in the activity of the stimulatory guanyl nucleotide-binding protein (Gs). Universal inhibition of agonist-stimulated adenylate cyclase activity did not occur, inasmuch as EGF did not reduce prostaglandin E2-enhanced enzyme activity. The influence of EGF on PTH action correlated with its effect in the UMR 106 cell population of promoting entry into the cell cycle. Morphological analysis with radioautography indicated that both EGF and PTH receptors could be colocalized to certain UMR 106 cells, but that each were more abundantly distributed over discrete UMR 106 cell types. Based on the distribution of [3H]thymidine incorporation, EGF receptors were predominantly found over rapidly proliferating cells, whereas PTH receptors were most densely distributed over more quiescent cells. The results indicate that EGF and PTH receptors are localized over specific types within the heterogeneous population of UMR 106 cells and suggest that EGF may reduce PTH action in these cultures by enhancing the proliferation of progenitor cells lacking PTH receptors and reducing differentiation in this cell population, which leads to PTH receptor-enriched target cells. EGF and PTH receptors may, therefore, be useful as probes to examine both functional interactions and differentiation pathways among cells in osteoblast models in vitro and perhaps in vivo.
Bernier
S M
SM
Calcium Research Laboratory, McGill University, Montreal, Quebec, Canada.
Rouleau
M F
MF
Goltzman
D
D
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002452:Cell Count; D015232:Dinoprostone / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D009994:Osmolar Concentration; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D010281:Parathyroid Hormone / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D019379:Teriparatide; D013936:Thymidine / Q000493:pharmacokinetics; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000067956:Adenylyl Cyclase Inhibitors; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D004815:Epidermal Growth Factor; D015232:Dinoprostone; D013936:Thymidine