Targeted overexpression of insulin-like growth factor I to osteoblasts of transgenic mice: increased trabecular bone volume without increased osteoblast proliferation.
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.
Zhao
G
G
Department of Medicine, University of Cincinnati College of Medicine, Ohio 45267, USA.
Monier-Faugere
M C
MC
Langub
M C
MC
Geng
Z
Z
Nakayama
T
T
Pike
J W
JW
Chernausek
S D
SD
Rosen
C J
CJ
Donahue
L R
LR
Malluche
H H
HH
Fagin
J A
JA
Clemens
T L
TL
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
D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I