One small step for mice
A NASA-funded study could lead to leaps for human health
Stephanie Carleton studies brittle bone disease in mice. Results could help humans who have the disease and astronauts who lose bone density on space missions. Researchers hope to learn whether exercise, such as walking on a treadmill, will improve bone density and strength in this mouse and others.
Small steps for mice could equal giant leaps for human health. Researcher Stephanie Carleton studies osteogenesis imperfecta (OI), commonly known as brittle bone disease, in mice. What she learns may help astronauts prevent bone loss and individuals with OI improve bone strength and density.
Osteogenesis imperfecta literally means imperfect bone formation. Individuals with OI have problems producing collagen. The lack of collagen makes their bones more susceptible to breaks. Charlotte Phillips, a genetics researcher and associate professor of biochemistry, says about one in 10,000 children has the disease. The mildest cases are often misdiagnosed.
In the case of astronauts, the lack of gravity in space causes a loss of bone density and bone strength. The longer the mission, the more pronounced the effects.
Carleton’s research could help both groups.
The National Space Biomedical Research Institute (NSBRI), a NASA-funded program, awarded Carleton a two-year post-doctoral grant that pays her salary while she conducts research with mentor Phillips. The Osteogenesis Imperfecta Foundation and the Leda J. Sears Trust Foundation are providing additional support for mice and supplies for the study.
Growing thicker bones
First, Carleton will breed mice for three groups: a control group with no genetic mutations, a group with OI and a group with OI and a mutation that inhibits myostatin, which regulates the growth of muscles. Decreasing myostatin produces bigger muscles in “buff mice.”
“Each one (group) has been characterized separately,” Carleton says. “So we know that these myostatin-deficient mice do have bigger muscles, they have improved bone strength, and when they exercise, their bones get that much better.”
Carleton will be looking at whether the myostatin deficiency helps increase bone production in individuals with OI.
“If we can get these guys to change their geometry and make thicker bones, overall they’re going to break less frequently,” Phillips says. “If you have a thin piece of Styrofoam, it snaps. A thick piece of Styrofoam is still Styrofoam, but it’s a little bit more work to get it to snap”
Researchers, from left, Bettina Weber, Charlotte Phillips and Stephanie Carleton study different aspects of brittle bone disease in mice.
Window of opportunity
By the age of 18, Phillips says, individuals will have acquired 90 percent of their maximal peak bone mass. This is important because an individual's peak bone mass determines their overall risk of developing osteoporosis.
“During adolescence, the body is able to lay down bone on the outer surface and on the inner surfaces. When you get older, the only place you’ll lay down bone is typically on the outer surface, so there’s a biological mechanism that’s at work in people and animals where they can maximize bone in their youth,” Phillips says.
Much like a tube, the thicker the walls, the stronger the bone.
The study will look at whether exercise can induce a higher peak bone mass during this “window of opportunity” in mice with OI and OI combined with myostatin deficiency. For exercise, the mice exercise run on a treadmill and swim.
Bettina Weber, a veterinarian doing postdoctoral work with Phillips and Carleton, also has done research that demonstrates that muscle tissue in mice with OI doesn’t look impaired or show atrophy or necrosis. This suggests that exercise is safe and should increase muscle size.
Carleton and Phillips also want to determine if exercise changes the shape of the bone, thus improving the strength. Stress can change the shape of a bone, and subtle geometric differences can make a big difference in the normal population.
“There’s a lot of evidence that a change of six to eight percent can make a hundred-fold difference in fatigue strength, so geometry has a big impact,” Phillips says.
For NASA, the information gleaned in the study may lead to use of myostatin-inhibiting therapies for astronauts. For individuals with OI, new therapies including exercise may be prescribed. The research could also have implications for people with osteoporosis.
“We should be able to tease out if exercise is good for mild disease or if exercise seems to work better for severe disease,” Phillips says. “We should be able to come up with some parameters or ranges of what’s possible. Hopefully, we’ll have some preliminary data by the end of the year.”