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H Tanaka, A Wakisaka, H Ogasa, S Kawai, and CT Liang

In order to establish the cellular basis for using growth factors as possible therapeutic agents for the age-dependent deficit in bone formation activity, we examined the individual and combined effects of IGF-I and/or platelet-derived growth factor (PDGF) on the gene expression of osteoblast-related markers in male rats. The expression of osteoblast markers was examined in the femurs of adult and old rats following marrow ablation, which amplifies gene expression activity. The mRNA levels of collagen(alpha1) (I) (COLI), alkaline phosphatase (AP), osteopontin (OP) and osteocalcin (OC) were significantly lower in the old as compared with the adult rats. To determine whether growth factors can abolish the age-related deficits in mRNA expression in old bone, PDGF and/or IGF-I were infused directly into the right femur for 5 days following marrow ablation. The contralateral femur was infused with vehicle only and used as a control. PDGF stimulated the expression of OP mRNA in both adult and old rats, whereas COLI, AP and OC mRNAs were not affected. IGF-I infusion did not have a significant effect on mRNA expression in adult rats. In contrast, treatment with IGF-I significantly enhanced the mRNA levels of COLI, AP and OP in old rats. To examine whether the combination of both factors could affect the expression of osteoblast markers synergistically, PDGF and IGF-I were infused together. In adult bones, the combined treatment with PDGF and IGF-I caused a slight increase in the level of OP gene expression but no change in AP, OC or COLI genes. Although neither IGF-I nor PDGF alone was effective in stimulating the expression of OC, the combined treatment in old bones enhanced OC expression significantly. The expression of COLI, AP and OP was also stimulated, but the stimulation was no different from that of IGF-I alone. In PDGF plus IGF-I treatment with a high dose, no dose-response effects were observed. Within the limits of the present study, it is suggested that IGF-I and, to a much lesser extent, PDGF may partially restore the deficit in the expression of osteoblast markers in old bones, and that the combination of both factors is slightly better than IGF-I alone in stimulating OC expression.