IN-VIVO AND IN-VITRO EFFECTS OF INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) ON FEMORAL MESSENGER-RNA EXPRESSION IN OLD RATS

The in vivo response of bone to IGF-I infusion in a marrow ablation mo del and the effect of IGF-I on bone marrow stromal cells in vitro was evaluated. IGF-I (25 ng/day), infused directly into femur, stimulated the expression of alkaline phosphatase, procollagen a, (I) and osteopo ntin mRNA, while osteocalcin mRNA was not affected. The dose dependenc y to IGF-I was bi-phasic, with stimulation at 25 and 50 ng but not at 150 ng/day. The effect of IGF-I was observed in the aged but not in th e adult rat femur. However, the elevated mRNA levels in old bones with IGF-I treatment were still below those observed in adult bones. The e ffect of IGF-I was also examined in cultured stromal cells. IGF-I (50 ng/ml) stimulates the expression of alkaline phosphatase, procollagen a, (I), osteopontin and osteocalcin mRNA in stromal cells from both ad ult and old rats. These results suggest that the lack of response of a dult bone to IGF-I in vivo was not due to the impaired response of the stromal cells to IGF-I. Differences in the responses of stromal cells from adult and old animals were noted. In the presence of serum (10%) , stromal cells from adult rats were stimulated to synthesize DNA at l ower levels of IGF-I than stromal cells from old animals. Our results show that IGF-I can stimulate mRNA expression of osteoblast markers in vivo in aged rats in a marrow ablation model and enhance DNA synthesi s and gene expression in cultured marrow stromal cells from old rats. Thus, it is possible that exogenous IGF-I could be beneficial in treat ing age-associated osteopenia.