Skeletal unloading induces biphasic changes in insulin-like growth factor-I mRNA levels and osteoblast activity.
To determine the local mechanisms involved in the effects of skeletal unloading on bone formation, we studied the temporal pattern of mRNA levels for insulin-like growth factor-I (IGF-I), IGF-I receptor type I (IGF-IR), and transforming growth factor beta receptor type II (TGF-betaRII) in relation to osteoblast phenotypic markers and osteoblast activity in hindlimb suspended rats. Skeletal unloading decreased bone volume and the mineralizing and osteoblastic surfaces at 4, 7, and 14 days in the tibial metaphysis, whereas the mineral appositional rate returned to normal at 14 days of suspension. RT-PCR analysis showed that skeletal unloading decreased type 1 collagen (Col 1) and osteocalcin (OC) mRNA levels in metaphyseal bone at days 4 and 7, and the levels returned to normal at 14 days of suspension. Unloading also decreased mRNA levels for IGF-I, IGF-IR, and TGF-betaRII at 4-7 days in the metaphyseal bone. However, IGF-I and IGF-IR levels rose above normal at 14 days of suspension. The biphasic changes in IGF-I mRNA levels were strongly correlated with Col 1 and OC mRNA levels. The associated biphasic pattern of IGF-I/IGF-IR expression, osteoblast markers, and osteoblast activity strongly suggests an important role for IGF-I signaling in the local effect of skeletal unloading on metaphyseal bone formation.
Drissi
H
H
Unit 349 INSERM, Cell and Molecular Biology of Bone and Cartilage, Paris.
Lomri
A
A
Lasmoles
F
F
Holy
X
X
Zerath
E
E
Marie
P J
PJ
D000818:Animals; D000943:Antigens, Differentiation; D002454:Cell Differentiation; D005269:Femur / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D009929:Organ Size; D010006:Osteoblasts / Q000166:cytology*; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D013977:Tibia / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D016474:Weight-Bearing
D000943:Antigens, Differentiation; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II