Spaceflight modulates insulin-like growth factor binding proteins and glucocorticoid receptor in osteoblasts

1 Faculty of Dentistry, Tokyo Medical and Dental University, Tokyo 113-8549; 2 Toray Research Center, Kamakura 248-78555; 3 National Space Development Agency, Tsukuba Space Center, Tsukuba 305-0047, Japan; and 4 National Aeronautics and Space Administration, Johnson Space Center, Houston, Texas 77058 Rat osteoblasts were cultured for 4 or 5 days during a Space Shuttle mission. After 20-h treatment with 1 ,25-dihydroxyvitamin D 3 , conditioned media were harvested and cellular DNA and/or RNA were fixed on board. The insulin-like growth factor binding protein (IGF BP)-3 levels in the media were three- and tenfold higher than in ground controls on the fourth and fifth flight days, as quantitated by Western ligand blotting and radioimmunoassay, respectively. The increased IGF BP-3 protein levels correlated with two- to threefold elevation of IGF BP-3 mRNA levels, obtained by reverse transcription-polymerase chain reaction. The IGF BP-5 mRNA levels in flight cultures were 33-69% lower than in ground controls. The IGF BP-4 mRNA levels in flight cultures were 75% lower than in ground controls on the fifth day but were not different on the fourth day. The glucocorticoid receptor mRNA levels in flight cultures were increased by three- to eightfold on the fourth and fifth days compared with levels in ground controls. These data suggest potential mechanisms underlying spaceflight-induced osteopenia. bone demineralization; osteoblast; microgravity