Michael Braukus Headquarters, Washington, D.C.

October 8, 1993 (Phone: 202/358-1979) Jane Hutchison Ames Research Center, Mountain View, Calif. (Phone: 415/604-9000) RELEASE: 93-181 SHUTTLE RAT EXPERIMENT YIELDS UNEXPECTED RESULTS Unexpected results from a recent Space Shuttle experiment on rats some day may lead to the discovery of the genes that direct bone cells to produce more bone. Last April's third Physiological and Anatomical Rodent Experiment (PARE-3) studied changes in the activity of bone-forming cells after 9 days of space flight. It also investigated whether these changes were reversed within 3 days of return to Earth. "We were totally surprised by some of the data from this flight experiment," said Dr. Emily Morey-Holton of NASA's Ames Research Center, Mountain View, Calif. Although she cautioned that much research remains to be done, Morey-Holton said the findings may accelerate the development of drugs to stimulate the production of new bone. Such medications could be important not only for astronauts on long-duration space missions but also for people on Earth suffering from bone-weakening disorders. At the end of the mission Morey-Holton and co-investigators Drs. Kim Westerlind and Russell Turner of the Mayo Clinic, Rochester, Minn., found a decrease in the production of certain chemical messages necessary for bone formation. This was followed within 24 hours by a dramatic increase in production of these chemicals. Levels again decreased within 72 hours after landing. The 40 percent decrease in chemical messages was seen in

cells on the outer surface of the lower leg bones (cortical bone). These messages direct bone-forming cells to produce proteins that are part of the process that results in formation of new bone. The investigators had expected this decrease since space flight is known to slow the rate of bone growth. - more -2"The big surprise was an unexpected 300 percent increase in these proteins within 24 hours after return to Earth," Morey-Holton said. "The response to reloading must have occurred almost immediately," she said. Walking or movement against the force of gravity is known as a load. Morey-Holton said re-exposure to Earth's gravity may have caused the cells to overcompensate for the slowed bone growth during space flight. "This suggests that the best time to learn about the initial steps in bone formation may be within 24 hours after space flight," Morey-Holton said. "The increase is probably large enough to allow scientists to establish a time course of events during the 24-hour period," she said. "It may be possible to tease out the genes involved in initiating cortical bone formation. If you know what the actual trigger is, you should be able to use that particular message to actually stimulate bone formation," she said. This, in turn, could lead to development of drug therapy. Because rats with unloaded hind limbs on Earth "showed virtually identical responses to the flight animals" on PARE-3, much additional research can be done in laboratories on the ground, she said. "This should accelerate the research, because it eliminates the years of waiting often necessary for a flight opportunity on the Space Shuttle." - end -