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 growt h factor-I (IGF-I) on skeletal cells are at present unclear. We have i nvestigated the role of glucose-6-phosphate dehydrogenase (G6PD) in th is mechanism and provide strong evidence that stimulation of G6PD acti vity is required for the growth promoting activities of IGF-I. IGF-I ( 10 ng/ml) significantly elevated G6PD activity in MG-63 human osteosar coma cells within 30 min which preceded the IGF-I induced DNA synthesi s in these cells. Inhibition of G6PD activity by epiandrosterone decre ased DNA synthesis in IGF-I stimulated MG-63 cells but this was partly overcome by the addition of a combination of the four deoxyribonucleo sides. IGF-I did not cause a general increase in cell metabolism as su ccinate dehydrogenase and iso-citrate dehydrogenase activity were not altered. Although IGF-I caused a significant increase in lactate dehyd rogenase activity this was not inhibited by epiandrosterone. The cultu re of metatarsals of 4-week-old rats with IGF-I (10 ng/ml) also stimul ated G6PD activity in osteoblasts lining the metaphyseal traheculae.