New research led by scientists at the Tokyo Institute of Technology provided data from real-time live-imaging of fluorescent signals derived from osteoblasts and osteoclasts of medaka fish after only one day of exposure to microgravity aboard the International Space Station (ISS). Findings from the study—entitled “Acute transcriptional up-regulation specific to osteoblasts/osteoclasts in medaka fish immediately after exposure to microgravity”—were published recently in Scientific Reports. The investigators are hopeful that their results will be useful not only for combating the effects of long-term space travel, but also elucidating the mechanisms of various bone-density disorders.
In their experiments, the Japanese researchers used four different double medaka transgenic lines focusing on up-regulation of fluorescent signals of osteoblasts and osteoclasts to clarify the effect of gravity on the interaction of the two bone cells. They also studied changes in the gene expression in the transgenic fish by transcriptome analysis. Interestingly, the researchers found increases in both osteoblast- and osteoclast-specific promoter-driven GFP and DsRed signals one day after launch and continued for up to eight days.
These findings suggest that exposure to microgravity induces an immediate, dynamic change in gene expression patterns for osteoblasts and osteoclasts. Namely, these experiments based on real-time imaging of medaka and transcriptome analysis could be the prelude to the establishment of a new scientific area of research in “gravitational biology.”
The live-imaging of fluorescence microscopy signals from the fish aboard the ISS were monitored remotely from Tsukuba Space Center in Japan. The microscopic images of osteoblasts showed the intensity of osterix– and osteocalcin-DsRed in pharyngeal bones had increased, one day after launch. This increased effect continued for eight days for osterix and five days for osteocalcin.
Concomitantly, for osteoclasts, the fluorescent signals observed from TRAP-GFP and MMP9-DsRed increased significantly on the fourth and sixth days after launch.
The fluorescent analysis was complemented by the use of transcriptome analysis to measure gene expression in the transgenic fish. The researchers stated that “HiSeq from pharyngeal bones of juvenile fish at day two after launch showed up-regulation of two osteoblast- and three osteoclast-related genes.”
“Gene ontology analysis for the whole-body revealed that transcription of genes in the category 'nucleus' was significantly enhanced; particularly, transcription regulators were more up-regulated at day two than at day six,” the authors wrote. “We identified five genes, c-fos, jun-B-like, pai-1, ddit4, and tsc22d3, which were up-regulated commonly in the whole-body at days two and six, and in the pharyngeal bone at day two.”
While the precise molecular mechanisms responsible for the loss of bone density are not yet fully understood, the current study is a significant step toward uncovering the mechanisms governing changes in bone structure immediately after the onset of microgravity, when bone loss is triggered. The findings imply that changes in osteoblasts and osteoclasts occur very soon after launch and may need to be quickly addressed for long-term space flight.