Aluminofluoride- and epidermal growth factor-stimulated DNA synthesis in MOB 3-4-F2 cells.
In attempt to study the mechanism of F(-)-induced, osteoblast-mediated bone formation, we tried to show the characteristics of Al-F complex-induced mitogenesis in osteoblastic cells. The MOB 3-4-F2 cell line, an osteoblast-like cell line derived from neonatal mouse calvaria, responded to F- (1-2 mM) combined with Al3+ and epidermal growth factor (EGF, 0.01-100 ng/ml) with increased DNA synthesis. Of the several types of Al-F complexes, AlF4- is thought to act as a mitogenic factor. On the other hand, NaF at high concentrations (greater than 2 mM) markedly decreased cell viability. The AlF(4-)-stimulated DNA synthesis at least with a delay of 48 hr, while EGF stimulated DNA synthesis within a few hours (4-6 hr). Both 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) and staurosporine, inhibitors of protein kinase C (PKC), further enhanced DNA synthesis in AlF(4-)-treated cells, whereas 12-O-tetradecanoyl-13-acetate (TPA), an activator of PKC, decreased the DNA synthesis. In EGF-treated cells, staurosporine and TPA, but not H-7, decreased DNA synthesis. In addition, indomethacin, an inhibitor of cyclooxygenase, partly inhibited the EGF-induced mitogenesis, which, however, was restored by addition of PGE2. AlF4-, as well as EGF, stimulated the release of arachidonic acid and its metabolites. Indomethacin failed to inhibit the AlF(4-)-induced mitogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Kawase
T
T
Department of Pharmacology, Niigata University School of Dentistry, Japan.
Orikasa
M
M
Suzuki
A
A
D000535:Aluminum / Q000494:pharmacology*; D017607:Aluminum Compounds; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005459:Fluorides / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D017607:Aluminum Compounds; D016718:Arachidonic Acid; D004815:Epidermal Growth Factor; D004247:DNA; D000535:Aluminum; D011493:Protein Kinase C; D005459:Fluorides; D007213:Indomethacin; C032311:aluminum fluoride