Mitogenic activity but not phenotype expression of rat osteoprogenitor cells in response to IGF-I is impaired in aged rats.

The age-related deficit in the dose response of osteoprogenitor cells to IGF-I was further investigated. As expected, the effective dose, but not the maximal effect, was shifted two orders of magnitude higher in old cells. In this paper, we examined whether this age-deficit can be attributed to an alteration in the expression and binding kinetics of IGF-I receptor. We showed that the levels of IGF-I receptor mRNA in cells, estimated by RT-PCR, were not significantly altered with age. Scatchard analysis showed that there were no significant differences in Kd and Bmax in cells from the two age groups. In a parallel study, we also showed that the expression of osteoblast phenotype markers was stimulated by IGF-I. However, no apparent differences in dose response curve were observed between two age groups. These results suggest that defect(s) in cell proliferation in aging may occur specifically in the signal transduction pathway between the receptor and the mitogenic response but not in the pathway associated with phenotype expression.