EFFECT OF AGE ON THE EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR-I, INTERLEUKIN-6, AND TRANSFORMING GROWTH-FACTOR-BETA MESSENGER-RNAS IN RAT FEMURS FOLLOWING MARROW ABLATION

The expression of insulin-like growth factor-I (IGF-I), interleukin-6 (IL-6), and transforming growth factor-beta(1) (TGF-beta(1)) mRNA in r at femurs was examined following marrow ablation, Northern blot analys is showed multiple transcripts of IGF-I, a major transcript of 1.3 kb and a minor one of 2.4 kb for IL-6 and a single band of 2.5 kb for TGF -beta(1), respectively, Examination of the temporal activation pattern showed IGF-I expression peaked at day 3 (150% over the basal level) a fter injury and preceded the maximal expression of procollagen alpha(1 )(I), osteopontin, alkaline phosphatase, and osteocalcin mRNAs, This s uggests that IGF-I is involved mainly in osteoblast development and bo ne formation, In contrast, IL-6 expression was elevated between days 3 and 9 (45-60% over the basal level), The sustained elevation of IL-6 expression at day 9 is consistent with the role for this cytokine in t he development of osteoclasts and bone resorption, The expression of T GF-beta(1) was not altered up to day 9 after marrow ablation, While th e temporal expression patterns of IGF-I and IL-6 mRNA did not differ b etween adult and old rats, the maximal level of IGF-I mRNA at day 3 wa s 72% higher in adult as compared to old bones, In contrast, the peak level of IL-6 mRNA at days 6-9 was 45% higher in old as compared to ad ult bones, Although the level of TGF-beta(1) mRNA did not change follo wing marrow ablation, levels of TGF-beta(1) were consistently higher i n old rats, Our results suggest that the impaired bone formation and e levated bone resorption in aged animals may be due in part to the redu ced expression of IGF-I and an overexpression of IL-6 in old bone.