EFFECTS OF MICROGRAVITY ON OSTEOBLAST GROWTH ACTIVATION
M. Hughes-Fulford1 and M.L. Lewis2
Laboratory of Cell Growth and Differentiation, Department of Veterans Affairs1, Department
of Medicine, University of California1, San Francisco, CA 94121 and Johnson
Research Center2 and Department of Biological Sciences2, University
of Alabama Huntsville Alabama 35899
ABSTRACT:
Spaceflight is an environmental condition where astronauts can lose up to 19% of weight
bearing bone during long duration missions. We used the MC3T3-E1 osteoblast to investigate
bone cell growth in microgravity (10-6 to 10-9 g). Osteoblasts were
launched on the STS-56 shuttle flight in a quiescent state with 0.5% fetal calf serum
(FCS) medium and growth activation was initiated by adding fresh medium with 10% FCS
during microgravity exposure. Four days after serum activation, the cells were fixed
before return to normal Earth gravity. Ground controls were treated in parallel with the
flight samples in identical equipment. On landing, cell number, cell cytoskeleton, glucose
utilization and prostaglandin synthesis in flight (n = 4) and ground controls (n = 4) were
examined. The flown osteoblasts grew slowly in microgravity with total cell number
significantly reduced (55 +/- 6 vs. 141 +/- 8 cells per microscopic field). The
cytoskeleton of the flight osteoblasts had a reduced number of stress fibers and a unique
abnormal morphology. Nuclei in the ground controls were large and round with punctate
Hoechst staining of the DNA nucleosomes. The flight nuclei were 30% smaller than the
controls (p<0.0001), oblong in shape, with fewer punctate areas. The cells activated in microgravity used significantly less glucose than ground controls (80.2 +/-0.7 vs. 50.3 +/- 3.7 mg of glucose/dl remaining in the medium) and had reduced prostaglandin E2 (PGE2) synthesis when compared to controls (57.3 +/- 17 vs. 138.3
+/- 41 pmoles/ml). The reduced glucose utilization and prostaglandin synthesis were a
function of the reduced cell growth since on a per cell basis the two measurements were
essentially identical. Taken together, these data suggest that lowered growth activation
in microgravity results in reduced growth, reduced glucose utilization, reduced
prostaglandin synthesis and significantly altered actin cytoskeleton in osteoblasts.
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