Mitogenic action of insulin-like growth factor-I on human osteosarcoma MG-63 cells and rat osteoblasts maintained in situ: the role of glucose-6-phosphate dehydrogenase.
The mechanisms involved in the mitogenic actions of insulin-like growth factor-I (IGF-I) on skeletal cells are at present unclear. We have investigated the role of glucose-6-phosphate dehydrogenase (G6PD) in this mechanism and provide strong evidence that stimulation of G6PD activity is required for the growth promoting activities of IGF-I. IGF-I (10 ng/ml) significantly elevated G6PD activity in MG-63 human osteosarcoma cells within 30 min which preceded the IGF-I induced DNA synthesis in these cells. Inhibition of G6PD activity by epiandrosterone decreased DNA synthesis in IGF-I stimulated MG-63 cells but this was partly overcome by the addition of a combination of the four deoxyribonucleosides. IGF-I did not cause a general increase in cell metabolism as succinate dehydrogenase and iso-citrate dehydrogenase activity were not altered. Although IGF-I caused a significant increase in lactate dehydrogenase activity this was not inhibited by epiandrosterone. The culture of metatarsals of 4-week-old rats with IGF-I (10 ng/ml) also stimulated G6PD activity in osteoblasts lining the metaphyseal trabeculae.
Farquharson
C
C
Bone Growth and Metabolism Unit, Rowett Research Institute, Bucksburn, Aberdeen, Scotland.
Milne
J
J
Loveridge
N
N
D000738:Androsterone / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008682:Metatarsal Bones; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D012516:Osteosarcoma / Q000201:enzymology / Q000473:pathology; D011506:Proteins / Q000378:metabolism; D051381:Rats; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D011506:Proteins; D007334:Insulin-Like Growth Factor I; D004247:DNA; D000738:Androsterone; D007770:L-Lactate Dehydrogenase; D007521:Isocitrate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D013385:Succinate Dehydrogenase