Distinct gene expression profiles in the femora of rats exposed to spaceflight, tail-suspension and denervation

Abstract

Unloading conditions occasionally cause muscle atrophy and osteopenia in humans and animals. In general, transcriptional alternations in bone and skeletal muscle cells mediate, respectively, the bone and muscle atrophy caused by unloading. In this study, we examined comprehensive gene expression in the femur of rats exposed to spaceflight (STS-58), tail-suspension and denervation (sciatic neurectomy), to characterize unloading-induced changes in bone gene expression. Interestingly, the transcriptional responses of bone cells to spaceflight were different from those to the other conditions: (i) the expression of bone formation markers was suppressed by spaceflight and denervation, but only spaceflight significantly inhibited the expression of bone resorption markers; (ii) 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), 74 (up, 72 genes; down, 2 genes) and 23 (up, 20 genes; down, 3 genes), respectively; (iii) spaceflight preferentially down-regulated the expression of signal transduction and gene-expression regulatory genes, especially GTP-binding protein-signaling molecules involved in bone formation; and (iv) only spaceflight up-regulated the expression of a predicted ubiquitin ligase, F-box protein 30. Our present study identifies novel key genes with which to elucidate further the mechanism of osteopenia caused by unloading, especially spaceflight.