In vivo and in vitro effects of insulin-like growth factor-I (IGF-I) on femoral mRNA expression in old rats.
The in vivo response of bone to IGF-I infusion in a marrow ablation model 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 alpha 1 (I) and osteopontin mRNA, while osteocalcin mRNA was not affected. The dose dependency 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 the adult rat femur. However, the elevated mRNA levels in old bones with IGF-I treatment were still below those observed in adult bones. The effect of IGF-I was also examined in cultured stromal cells. IGF-I (50 ng/ml) stimulates the expression of alkaline phosphatase, procollagen alpha 1 (I), osteopontin and osteocalcin mRNA in stromal cells from both adult and old rats. These results suggest that the lack of response of adult 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 lower 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 synthesis and gene expression in cultured marrow stromal cells from old rats. Thus, it is possible that exogenous IGF-I could be beneficial in treating age-associated osteopenia.
Tanaka
H
H
Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD.
Quarto
R
R
Williams
S
S
Barnes
J
J
Liang
C T
CT
D000375:Aging / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D001851:Bone Diseases, Metabolic / Q000188:drug therapy; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005269:Femur / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D010006:Osteoblasts / Q000187:drug effects*; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D053495:Osteopontin; D011347:Procollagen / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism
D011347:Procollagen; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D015675:Osteocalcin; D053495:Osteopontin; D007334:Insulin-Like Growth Factor I; D000469:Alkaline Phosphatase; D013936:Thymidine