Altered skeletal pattern of gene expression in response to spaceflight and hindlimb elevation.
Spaceflight leads to osteopenia, in part by inhibiting bone formation. Using an animal model (hindlimb elevation) that simulates the weightlessness of spaceflight, we and others showed a reversible inhibition of bone formation and bone mineralization. In this study, we have measured the mRNA levels of insulin-like growth factor I (IGF-I), IGF-I receptor (IGF-IR), alkaline phosphatase, and osteocalcin in the tibiae of rats flown aboard National Aeronautics and Space Administration Shuttle Flight STS-54 and compared the results with those obtained from their ground-based controls and from the bones of hindlimb-elevated animals. Spaceflight and hindlimb elevation transiently increase the mRNA levels for IGF-I, IGF-IR, and alkaline phosphatase but decrease the mRNA levels for osteocalcin. The changes in osteocalcin and alkaline phosphatase mRNA levels are consistent with a shift toward decreased maturation, whereas the rise in IGF-I and IGF-IR mRNA levels may indicate a compensatory response to the fall in bone formation. We conclude that skeletal unloading during spaceflight or hindlimb elevation resets the pattern of gene expression in the osteoblast, giving it a less mature profile.
Bikle
D D
DD
Department of Medicine, University of California, San Francisco.
Harris
J
J
Halloran
B P
BP
Morey-Holton
E
E
D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D005786:Gene Expression Regulation; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008297:Male; D015675:Osteocalcin / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000235:genetics; D013026:Space Flight; D014893:Weightlessness
D012333:RNA, Messenger; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D000469:Alkaline Phosphatase