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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 μg/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.
Journal of Bone and Mineral Research – Oxford University Press
Published: Sep 1, 2002
Keywords: insulin‐like growth factor I; bone formation; osteoblast progenitors; mice; ovariectomy
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