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EFFECT OF INFLIGHT 1-G ON MICROGRAVITY INHIBITION OF GENE INDUCTION OF GROWTH FACTORS, ONCOGENES, AND COX-2.  M. Hughes-Fulford Lab of Cell Growth, UCSF, NCIRE and VAMC, San Francisco, CA

     It has been previously demonstrated both in vivo and in vitro that osteoblast growth is reduced in microgravity.  Fetal calf sera (FCS) stimulates expression of several growth factors in normal Earth gravity.  In this study, we present new data on osteoblast growth factor induction by FCS in microgravity.  Early passage MC3T3-E1 cells were launched on STS-76, 81 and 84 in a quiescent state in Biorack hardware. FCS activation occurred in orbit approximately 19 hours after launch.  All data are derived using semi-quantative rtPCR from triplicate samples for each gene studied. Cyclophilin or18s mRNA expression was used to normalize expression of the genes.  Analyses of osteoblast gene expression show a significant diminished induction of TGFb, TGFb, c-myc, bcl2 and PCNA in microgravity.  TGFb, c-myc, and bcl2 expression was recovered in flight samples grown on the onboard 1-G centrifuge.  Expression levels of EGFr, 18s, and cyclophilin were constitutive and unchanged by microgravity.  Although initial FCS induction of cox-2 and its product PGE₂ were relatively high in flown osteoblasts 3h after activation, cox-2 expression was significantly lower in microgravity samples after 24 hours.  In conclusion, FCS mediated induction of six growth related genes was inhibited in microgravity, expression of four of these genes was recovered by artificial gravity in orbit. These data suggest that much of the bone loss observed in astronauts during long-term spaceflight may be ameliorated by the presence of an onboard gravity facility on the Mars Vehicle.

     (Supported by NASA grants: NAG-2-1086; NAG-2-1286)