AJP - Endocrinology and Metabolism, Vol 267, Issue 6 E822-E827, Copyright © 1994 by American Physiological Society
Altered skeletal pattern of gene expression in response to spaceflight and hindlimb elevation
D. D. Bikle, J. Harris, B. P. Halloran and E. Morey-Holton
Department of Medicine, University of California, San Francisco.
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.
