vendredi 15 septembre 2017

Using Transparent Fish to Study Denser Bones

ISS - Medaka Osteoclast Mission patch.

Sept. 15, 2017

Astronauts have dealt with loss of bone density during space flight since space travel began. Recent research aboard the International Space Station looked at how osteoclasts, cells that normally break down bone tissue for normal replacement, influence this loss.

Image above: Flight Engineer Koichi Wakata works to activate the Multi-Purpose Small Payload Rack (MSPR) Hub unit and install the Medaka Chamber in the fluorescent microscope for observation of a Medaka sample. Image Credit: NASA.

Now a follow-up investigation, Medaka Osteoclast 2, examines the molecular mechanisms that develop osteoclasts, using live fish in space. These Medaka fish have translucent bodies and, for this investigation, a genetic modification that marked osteoblasts and osteoclasts with fluorescent proteins so that researchers can observe cellular and genetic changes during space flight.

Scientists sent similar fish to the space station in 2014 for live taping by Astronaut Koichi Wakata during the first use of a fluorescence microscope on an animal aboard the space station. The taping revealed enhanced signals of both osteoclasts and osteoblasts, cells that synthesize bone tissue, within two days of launch.

Image above: The JAXA Microscope in the Japanese Experiment Module. Image Credit: JAXA.

“We examined the fluorescent signals in living Medaka fish and surprisingly, observed up-regulation of osteoblast as well as osteoclast signals,” said principal investigator Akira Kudo, Tokyo Institute of Technology. Researchers saw enhanced intensity of the fluorescent signals in the entire body of the fish, but focused on the pharyngeal or jaw bone region, which has high bone turnover and high sensitivity to microgravity. “Osteoblasts and osteoclasts are most closely associated with bones and teeth. These mineralized tissues show the most sensitivity to gravity since they have the highest density of any tissue in the body.” 

Scientists also identified five specific genes related to how these cells respond to gravity, all five closely correlated with glucocorticoid receptors in mitochondria in the cell. Glucocorticoids are steroid hormones involved in glucose metabolism, and glucocorticoid receptors may play a part in osteoclast activation.

For the current investigation, astronauts will tape the Medaka fish live aboard the space station, allowing investigators to observe changes in fluorescent signals in real-time remotely from Tsukuba Space Center in Japan. Post-flight, the researchers will analyze changes in the microscopic anatomy and gene expression in the pharyngeal bone and jawbone of the fish.

Image above: A representation of how researchers on the ground conduct live-imaging under microgravity. Image Credit: Tokyo Institute of Technology.

Kudo, co-investigator Masahiro Chatani and colleagues recently published a paper in Nature Scientific Reports outlining the microgravity-induced changes observed in the gene expression levels of osteoblasts and osteoclasts in medaka jawbones. Evidence indicates that the basic molecular mechanism of osteoclasts is the same in mammals as in fish and that interaction with osteoblasts plays a crucial role.

“Initially we expected up-regulation of osteoclast signal only,” Kudo said. “Now, we know both osteoblasts and osteoclasts are activated under microgravity. That raises the question, what is the relationship between osteoblasts and osteoclasts under microgravity?”

Special Medaka chambers in KIBO, or the Japanese Experiment Module on the space station, make it possible to place the fish under a fluorescence microscope for live imaging. The Microscope Observation System consists of a microscope, power supply, and control unit. It is manipulated under the same measurement conditions in space and on the ground. An additional step to the experiment determined that the hypergravity experienced during launch into space had no detectable effect on fluorescent signals from the fish.

Image above: Observing bone metabolism under microgravity through increase of fluorescent signals of osteoblasts and osteoclasts in Medaka. Image Credits: Tokyo Institute of Technology/JAXA.

Results of this latest joint research by the Tokyo Institute of Technology and JAXA will clarify the molecular mechanism behind decreased bone mineral density in space. This will help scientists develop more effective ways to prevent bone density loss on future space missions. The results also may advance development of new drugs and treatments for people experiencing bone loss caused by bed rest, limited mobility, and age-related osteoporosis.

The next step, according to Kudo, is to find direct evidence that the glucocorticoid receptor and its signals in microgravity conditions are involved in bone loss during space flight. For that, more transparent fish may get to fly in space.

Related links:

Nature Scientific Reports:

Medaka Osteoclast 2:


Space Station Research and Technology:

International Space Station (ISS):

Images (mentioned), Text, Credits: NASA/Kristine Rainey/JSC/Melissa Gaskill.

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