Insulin-like growth factor I effect on the number of osteoblast progenitors is impaired in ovariectomized mice

Because insulin-like growth factor (IGF) I is an important regulator of bone formation, we proposed the hypothesis that IGF-I could contribute in regulating the number of osteoblast progenitors (colony-forming unit fibroblast with ALP activity [CFU-F/ALP(+)]). To test ex vivo and in vivo effects of IGF-I on the number of CFU-F/ALP+, bone marrow cells (BMCs) derived from normal mice, growth hormone (GH)-deficient lit/lit mice, or ovariectomized (OVX) mice were cultured and the CFU-F/ALP+ number was counted. Ex vivo treatment of IGF-I increased the CFU-F/ALP+ number in a dose-dependent manner compared with vehicle-treated control cultures. The CFU-F/ALP+ number was decreased by 20% (p < 0.01; n = 7-9) in GH-deficient lit/lit mice compared with age-matched control mice. Four weeks after OVX or sham operation, IGF-I (2 mug/g body wt) or vehicle was administered twice on day 1, and 5 days later, BMCs were removed from the femur and cultured for 10 days (n = 9-10 per group). IGF-I administration increased the CFU-F/ALP+ number by 63% (p < 0.01) and 19% (NS), respectively, in sham-operated (sham) and OVX mice compared with the vehicle-treated control group. The serum IGF-I level was similar in OVX mice compared with sham mice; this finding is different from that found in rats in which OVX increases the serum IGF-I level. This study showed that IGF-I is an important regulator of osteoblast-progenitor number in the BMCs of mice both ex vivo and in vivo and that the IGF-I response to increase the number of osteoblast progenitors was impaired in OVX mice.