EFFECT OF LOCALLY INFUSED IGF-I ON FEMORAL GENE-EXPRESSION AND BONE TURNOVER ACTIVITY IN OLD RATS

Previously, we showed that the age-dependent deficit in bone formation activity can be attributed in part to a decline in local expression o f insulin-like growth factor I (IGF-I) and altered mitogenic response of old osteoprogenitor cells to IGF-I. To establish the cellular basis for using IGF-I as a possible therapeutic agent for osteoporosis, we examined the effect of locally infused (50 ng/day for 14 days) on the expression of osteoblast-related genes in femurs of old rats. Northern and dot blot analyses showed that the expression of procollagen (I), osteopontin, alkaline phosphatase, and osteocalcin was increased 0.4- to 1.5-fold in IGF-1-treated femurs as compared with control femurs. H istomorphometric analyses were carried out in parallel experiments to assess the changes in bone remodelling activity. Trabecular bone volum e, trabecular number, and trabecular thickness were increased 56%, 29% , and 23%, respectively, whereas trabecular separation was reduced 26% by IGF-1 treatment. IGF-I treatment increased significantly the osteo id volume, osteoid surface, osteoblast number, and osteoblast surface. Mineralizing surface and mineral apposition rate, kinetic indices of bone formation, were also stimulated by IGF-I treatment. The bone form ation rate was stimulated 81% in IGF-I-treated femurs as compared with control femurs. In contrast, eroded surface and osteoclast surface, p arameters associated with bone resorption, were not affected by IGF-I treatment. These findings suggest that local administration of IGF-I i nto femurs of old rats can stimulate the expression of matrix proteins and improve trabecular bone status by stimulating bone formation with out any appreciable effect on bone resorption.