Microgravity induces “dynamic alteration of gene expressions in osteoblasts and osteoclasts”

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Space travel is associated with a loss of bone mineral density

Live-imaging and transcriptome analysis of medaka fish transgenic lines has revealed that exposure to microgravity can lead to the immediate alteration of cells responsible for bone structure formation. These findings, published in Scientific Reports, are important for assessing the effects microgravity on long term human space missions.

Space travel in a reduced gravity environment can have lasting effects on the body. For example, researches clearly show that astronauts undergo a significant drop in bone mineral density during space missions, but the precise molecular mechanisms responsible for such changes in bone structure are unclear.

Life in so-called ‘microgravity’ environments—where the force of gravity is considerably less than on Earth—can cause significant problems for the human body. Astronauts who spend a number of months in space have been shown to suffer from reduced bone mineral density.

Akira Kudo from Tokyo Tech, Tokyo, Japan, and others performed remote live-imaging to look at fluorescent signals derived from osteoblasts and osteoclasts of medaka fish after only one day of exposure to microgravity aboard the International Space Station. They found increases in both osteoblast and osteoclast specific promoter-driven GFP and DsRed signals at one day after launch, which continued for up to eight days.

In their experiments, the team 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 osteoblast-osteoclast. They also studied changes in the gene expression in the transgenic fish by so-celled transcriptome analysis.

These findings suggest that exposure to microgravity induced an immediate “dynamic alteration of gene expressions in osteoblasts and osteoclasts.” According to a press release, these experiments could be the prelude to the establishment of a new scientific area of research—“gravitational biology”.

The live-imaging of fluorescence microscopy signals from fish aboard the space station were monitored remotely from Tsukuba Space Center in Tsukuba, Japan.

Live-imaging of osteoblasts showed that the intensity of osterix- and osteocalcin-DsRed in pharyngeal bones increased one day after launch. This increased effect continued for eight days for osterix and five days for osteocalcin.

In the case of 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 complimented by using transcriptome analysis to measure gene expression in the transgenic fish. The researchers state that, “HiSeq from pharyngeal bones of juvenile fish at day two after launch showed up-regulation of two osteoblast- and three osteoclast- related genes”.

Transcription of the “nucleus” was also found to be significantly enhanced based on whole body gene ontology analysis of RNA-Seq, with the researchers observing more up-regulated transcription-regulators at day two compared with day six.

Finally, Kudo and the team identified five genes: (c-fos and jun-b, pai-1 and ddit4, and tsc22d3) that were all up-regulated in the whole-body on days two and six, and in the pharyngeal bone on day two.

The precise molecular mechanisms responsible for loss of bone density are not yet fully understood.

The current study by Kudo and his team is a step towards uncovering the mechanisms governing changes in bone structure immediately after the onset of microgravity, when bone loss is triggered. By remote live-imaging from Tsukuba Space Center of the behaviour of medaka on board the international space station, they found significant increases in both osteoblast and osteoclast specific promoter-driven GFP and DsRed after exposure to microgravity. The findings imply that changes in osteoblasts and osteoclasts occur very soon after launch.

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