Limiting a specific maternal protein in
pregnant mice with osteogenesis imperfecta resulted in offspring with
stronger, denser bones, suggested researchers at the University of Missouri School of
Medicine. The finding might one day provide a new
therapeutic approach to treating brittle bone disease.
Osteogenesis imperfecta, also known as brittle bone disease, is a
genetic disorder that causes bones to break easily. Severe cases of the
disease can result in hundreds of fractures during a person's lifetime
or even death.
‘The offspring from myostatin-deficient mothers with transplanted embryos had stronger, denser bones when they grew up than mice with the same genetic makeup from osteogenesis imperfecta females.’
"Osteogenesis imperfecta is caused by the body's inability to make
strong bones because of mutations affecting the production of the
protein known as collagen," said Charlotte Phillips, associate
professor of biochemistry and child health at the MU School of Medicine
and a senior author of the study.
"No cure exists; however, we know from
previous research that the prenatal environment can have a lasting
effect on cardiovascular and metabolic health into adulthood. We studied
whether bone health of mice could be improved by optimizing the
environment within the womb."
Myostatin is a protein that limits muscle growth. However, exercise
causes myostatin levels to decrease - which is good because it allows
muscle tissue to develop, Phillips said. Increased muscle tissue results
in stronger bones. In the study, Phillips and her team decreased
maternal myostatin levels to see if this would increase bone strength in
offspring with osteogenesis imperfecta.
Using mice with brittle bone disease, the MU researchers were able
to identify the female as responsible for offspring bone health. The
team also confirmed that female mice deficient in myostatin had
offspring with stronger bones.
"The third part of our study really confirmed our initial
hypothesis," said Laura Schulz, associate professor of
obstetrics, gynecology and women's health at the MU School of Medicine
and a senior author of the study.
"50 to 80% of bone density
is predicted by genetics. To see if we could reverse this trend, we
transplanted embryos from female mice with osteogenesis imperfecta into
the wombs of female mice deficient in myostatin. The offspring from
myostatin-deficient mothers with transplanted embryos had stronger,
denser bones when they grew up than mice with the same genetic makeup
from osteogenesis imperfecta females."
"Humans achieve 90% of their peak bone mass by age 19,"
Phillips said. "To approximate this timeframe with mice, we re-evaluated
their bone strength and density four months after birth. In each case,
the mice with stronger, denser adult bones were those whose fetal
development involved females deficient in the protein myostatin. This
finding shows that the environment within the womb affects bone
development not only at birth, but into adulthood."
Both researchers believe that their work represents a paradigm shift
in understanding and possibly treating osteogenesis imperfecta. The
researchers also feel that their findings may prove beneficial to
reducing the risk of other bone diseases such as osteoporosis later in
life for many others. However, more research is needed.
"The intrauterine environment is important to bone health," Schulz
said. "For parents with osteogenesis imperfecta, we may be able to
reduce the severity of their unborn child's disease through prenatal
treatment. This also may be true for reducing the instances and severity
of other bone diseases."