1. In vivo and in vitro effects of insulin-like growth factor-I (IGF-I) on femoral mRNA expression in old rats
- Author
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C.T. Liang, Rodolfo Quarto, S. Williams, J. Barnes, and H. Tanaka
- Subjects
Male ,Aging ,Physiology ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Messenger ,genetics/metabolism ,Wistar ,Bone Marrow ,Northern ,Osteopontin ,Femur ,Insulin-Like Growth Factor I ,Cells, Cultured ,Cultured ,biosynthesis/metabolism ,biology ,Blotting ,Osteoblast ,drug effects/genetics ,drug therapy ,medicine.anatomical_structure ,Cytokine ,Osteocalcin ,Alkaline phosphatase ,Bone Diseases ,Drug ,Procollagen ,medicine.medical_specialty ,Histology ,Stromal cell ,Cells ,Sialoglycoproteins ,Bone Marrow Cells ,In Vitro Techniques ,Dose-Response Relationship ,pharmacology/therapeutic use ,In vivo ,Internal medicine ,medicine ,Animals ,RNA, Messenger ,Rats, Wistar ,cytology/drug effects ,Osteoblasts ,Dose-Response Relationship, Drug ,Animal ,Blotting, Northern ,Alkaline Phosphatase ,Rats ,Bone Diseases, Metabolic ,Disease Models, Animal ,Endocrinology ,Gene Expression Regulation ,drug effects ,Disease Models ,biology.protein ,RNA ,Bone marrow ,metabolism, Alkaline Phosphatase ,genetics/metabolism, Animals, Blotting ,Northern, Bone Diseases ,Metabolic ,drug therapy, Bone Marrow Cells, Bone Marrow ,drug effects/metabolism, Cells ,Cultured, Disease Models ,Animal, Dose-Response Relationship ,Drug, Femur ,drug effects/metabolism, Gene Expression Regulation ,drug effects/genetics, Insulin-Like Growth Factor I ,pharmacology/therapeutic use, Male, Osteoblasts ,drug effects, Osteocalcin ,genetics/metabolism, Osteopontin, Procollagen ,genetics/metabolism, RNA ,biosynthesis/metabolism, Rats, Rats ,Wistar, Sialoglycoproteins ,genetics/metabolism, Stromal Cells ,cytology/drug effects, Thymidine ,metabolism ,Stromal Cells ,drug effects/metabolism ,Thymidine - Abstract
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 ∝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 ∝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.
- Published
- 1994