title: Targeted overexpression of insulin-like growth factor I to osteoblasts of transgenic mice: increased trabecular bone volume without increased osteoblast proliferation.
abstract: Insulin-like growth factor I (IGF-I) is an important growth factor for bone, yet the mechanisms that mediate its anabolic activity in the skeleton are poorly understood. To examine the effects of locally produced IGF-I in bone in vivo, we targeted expression IGF-I to osteoblasts of transgenic mice using a human osteocalcin promoter. The IGF-I transgene was expressed in bone osteoblasts in OC-IGF-I transgenic mice at high levels in the absence of any change in serum IGF-I levels, or of total body growth. Bone formation rate at the distal femur in 3-week-old OC-IGF-I transgenic mice was approximately twice that of controls. By 6 weeks, bone mineral density as measured by dual energy x-ray, and quantitative computed tomography was significantly greater in OC-IGF-I transgenic mice compared with controls. Histomorphometric measurements revealed a marked (30%) increase femoral cancellous bone volume in the OC-IGF-I transgenic mice, but no change in the total number of osteoblasts or osteoclasts. Transgenic mice also demonstrated an increase in the osteocyte lacunea occupancy, suggesting that IGF-I may extend the osteocyte life span. We conclude that IGF-I produced locally in bone osteoblasts exerts its anabolic effect primarily by increasing the activity of resident osteoblasts.
authors.affiliation: Department of Medicine, University of Cincinnati College of Medicine, Ohio 45267, USA.
authors.forename: G
authors.initials: G
authors.lastname: Zhao
authors.forename: M C
authors.initials: MC
authors.lastname: Monier-Faugere
authors.forename: M C
authors.initials: MC
authors.lastname: Langub
authors.forename: Z
authors.initials: Z
authors.lastname: Geng
authors.forename: T
authors.initials: T
authors.lastname: Nakayama
authors.forename: J W
authors.initials: JW
authors.lastname: Pike
authors.forename: S D
authors.initials: SD
authors.lastname: Chernausek
authors.forename: C J
authors.initials: CJ
authors.lastname: Rosen
authors.forename: L R
authors.initials: LR
authors.lastname: Donahue
authors.forename: H H
authors.initials: HH
authors.lastname: Malluche
authors.forename: J A
authors.initials: JA
authors.lastname: Fagin
authors.forename: T L
authors.initials: TL
authors.lastname: Clemens
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D001846:Bone Development / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D005269:Femur / Q000033:anatomy & histology*; D015870:Gene Expression; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D015675:Osteocalcin / Q000235:genetics; D010011:Osteocytes / Q000166:cytology; D019076:Transgenes / Q000502:physiology
chemical_list: D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I