Study Finds Protein In Womb Plays Lifelong Role In Bone Health In Mice

Researchers at the University of Missouri School of Medicine found that limiting a specific maternal protein in pregnant mice with osteogenesis imperfecta resulted in giving birth to pups with stronger, denser bones. Osteogenesis imperfecta (brittle bone disease), is a genetic disorder that makes bones to so fragile that they break easily.

Severe cases of the condition can lead to hundreds of fractures in a lifetime or even death. However, the finding of the new study might one day provide a new therapeutic approach to treating brittle bone disease.

"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," senior author and associate professor of biochemistry and child health at the MU School of Medicine, Charlotte Phillips, Ph.D. said.

She added that although there is no known cure for the condition, previous studies on the topic have revealed that the prenatal environment could have a long-lasting impact on metabolic and cardiovascular health into adulthood. This made the researchers to investigate whether the bone health of mice could be improved by optimizing the environment within the womb, Eurekalert.

She continued to say that myostatin is a protein that limits the growth of muscle but its levels are reduced by exercise which is good because it allows muscle tissue to develop as more muscle tissue results in stronger bones. In the study, the researchers reduced maternal myostatin levels to see if it will improve bone strength in offspring with osteogenesis imperfecta.

While experimenting on the mice with brittle bone disease, they were able to find that the female is responsible for the offspring's bone health and also discover that female mice deficient in myostatin had offspring with stronger bones. They also found that 50 to 80 percent of bone density is predicted by genetics and to reverse this trend, the study authors transplanted embryos from female mice with osteogenesis imperfecta into the wombs of female mice deficient in myostatin.

The pups transplanted into myostatin-deficient mothers had stronger, denser bones when they grew up than mice with the same genetic makeup from osteogenesis imperfecta females. Since humans achieve 90 percent of bone mass by the age of 19, the researchers, to approximate the timeframe with mice, re-evaluated their bone strength and density four months after birth, Science Daily.

They found that mice with stronger, denser bones were those whose fetal development involved females deficient in the protein myostatin, thus, showing that the environment within the womb influences bone development into adulthood not only at birth.

The study authors believe that their findings represent a paradigm shift in understanding and possibly treating osteogenesis imperfecta. They also suggest that their result could be beneficial in reducing the risk of other bone diseases later in life for many others, but they stated that further studies are necessary to better understand the condition. The researchers published their findings in Proceedings of the National Academy of Sciences.