IGF-binding protein-5 stimulates osteoblast activity and bone accretion in ovariectomized mice.
Insulin-like growth factor binding protein-5 (IGFBP-5) is an osteoblast secretory protein that becomes incorporated into the mineralized bone matrix. In osteoblast cultures, IGFBP-5 stimulates cell proliferation by an IGF-independent mechanism. To evaluate whether IGFBP-5 can stimulate osteoblast activity and enhance bone accretion in a mouse model of osteoblast insufficiency, daily subcutaneous injections of either intact [IGFBP-5 (intact)] or carboxy-truncated IGFBP-5 [IGFBP-5-(1--169)] were given to ovariectomized (OVX) mice for 8 wk. Femur and spine bone mineral density (BMD), measured every 2 wk, showed early and sustained increases in response to IGFBP-5. Bone histomorphometry of cancellous bone showed significant elevations in the bone formation rate in both the femur metaphysis [IGFBP-5- (1)] only) and spine compared with OVX controls. IGFBP-5 also stimulated osteoblast number in the femur IGFBP-5-(1--169) only) and spine. These data indicate that IGFBP-5 effectively enhances bone formation and bone accretion in OVX mice by stimulating osteoblast activity. The finding that IGFBP-5-(1--169) is bioactive in vivo indicates that the carboxy-terminal portion is not required for this bone anabolic effect.
Andress
D L
DL
Department of Medicine, University of Washington, Seattle 98105, USA. dandress@u.washington.edu
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D002452:Cell Count; D004967:Estrogens / Q000172:deficiency; D005260:Female; D005269:Femur / Q000166:cytology / Q000187:drug effects; D007279:Injections, Subcutaneous; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000008:administration & dosage* / Q000031:analogs & derivatives; D051379:Mice; D008809:Mice, Inbred C3H; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010052:Ovariectomy; D013131:Spine / Q000166:cytology / Q000187:drug effects
D004967:Estrogens; D018975:Insulin-Like Growth Factor Binding Protein 5