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Expression Profile of Rat Bone Genes Responsive to Spaceflight.  Y. Onishi1, N. Suzue2, T. Ogawa2, K. Hirasaka1, H. Furouchi1, N. Yasui2, K. Ishidoh3, K. Kishi1 and T. Nikawa1.  1Dept. of Nutrition, Univ. of Tokushima School of Medicine, 2Dept. of Orthopedics, Univ. of Tokushima School of Medicine, and 3Dept. of Institute for Health Sciences, Univ. of Tokushima Bunri, Tokushima, JAPAN.

   Osteopenia has been reported to occur in humans and animals during unloading conditions, such as spaceflight, tail-suspension and denervation.  By using DNA microarray analysis, we previously examined gene expression profile in rat gastrocnemius muscle atrophied by these unloading conditions, suggesting that unloading, especially spaceflight, induced the significant transcriptional alternation of skeletal muscle cells (Nikawa et al. FASEB J. 18: 522-524, 2004).  Based on these findings, we reasoned that osteopenia was also induced by unloading through the transcriptional alternation of bone cells.  In this study, we examined comprehensive gene expression in femur of rats exposed to unloading conditions by using the same technique.  The numbers of the genes that exhibited more than a five-fold change in expression level in response to spaceflight, tail-suspension, and denervation were 122 (Up, 14 genes; Down, 108 genes), 75 (Up, 73 genes; Down, 2 genes), and 23 (Up, 20 genes; Down, 3 genes), respectively.  The expression of femur gene was more suppressed by spaceflight, compared with other conditions.  Bone and skeletal muscle are similarly atrophied by unloading.  Interestingly, our present results showed that the transcriptional responses of bone cells to unloading conditions were different from those of skeletal muscle cells and suggest that unloading may cause the atrophy in bone in distinct mechanism from those in skeletal muscle.  In bone, the expression of G protein molecules in signal transduction was preferentially inhibited by spaceflight.  The down-regulation of G protein-mediated signaling may play an important role in the reduced transcription and cell response in bone, which consequently cause osteopenia under weightlessness.

(Supported by JAXA and Japan Space Forum)