title: Insulin-like growth factor I effect on the number of osteoblast progenitors is impaired in ovariectomized mice.
abstract: 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 microg/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.
authors.affiliation: Musculoskeletal Disease Center, JL Pettis Veterans Administration Medical Center, Loma Linda, California 92357, USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kasukawa
authors.forename: Lisa
authors.initials: L
authors.lastname: Stabnov
authors.forename: Naohisa
authors.initials: N
authors.lastname: Miyakoshi
authors.forename: David J
authors.initials: DJ
authors.lastname: Baylink
authors.forename: Subburaman
authors.initials: S
authors.lastname: Mohan
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D003114:Colony-Forming Units Assay; D005260:Female; D013006:Growth Hormone / Q000172:deficiency; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008954:Models, Biological; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010052:Ovariectomy; D011966:Receptors, LHRH / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology
chemical_list: D011966:Receptors, LHRH; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D000469:Alkaline Phosphatase