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Jinzeng Yang leads a team that is pioneering gene research that promotes skeletal reformation and could lead to treatments for osteoporosis.
PHOTO COURTESY UNIVERSITY OF HAWAII
CINDY ELLEN RUSSELL / CRUSSELL@STARADVERTISER.COM
Lead researcher Jinzeng Yang has generated an animal model for studying skeletal formation and osteoporosis. At left, by altering the gene GDF11 in mice, an extra set of ribs, shown in the circular area, is produced.
University of Hawaii researchers have successfully depressed a specific gene in mice, which could help shed light on fatal skeletal deformations in humans and unearth ways to fight osteoporosis.
Lead researcher Jinzeng Yang, a UH associate professor of animal molecular biology, believes it is the first time anyone has partially suppressed growth differentiation factor 11, a gene also known as GDF11.
The striking result: One vertebra in the mice — part of the small bones of the upper spine — was transformed into a larger bone with a set of ribs.
Former UH graduate student Zicong Li and UH researchers Miyuri Kawasumi, Baoping Zhao, Stefan Moisyadi and Yang collaborated on the paper, which was published in November as the cover story in the international journal Molecular Reproduction and Development.
Yang said his lab works to better understand GDF11, a gene critical to skeletal formation and the dynamics of bone reformation.
The human body is made up of about 20,000 genes, and scientists are still trying to learn the exact function of many of them. Scientists sometimes determine a gene’s function by turning off the gene, then watching how the animal is changed.
The problem with that method is that the change can lead to stillbirth or termination of the fetus’ development.
"So many of the genes deal with embryonic development," Yang said. "If you remove that (gene), there’s no animal born. You cannot figure out (the gene’s function after birth)."
That was the problem with GDF11 until Yang and his fellow researchers partially suppressed the gene, allowing it to function enough to keep the animal alive through birth, grow into adulthood and produce several generations of offspring with the same modified DNA.
The researchers "knocked down" GDF11 by changing the ratio at which it produced proteins and propeptides, the compounds that carry out the gene’s function and reduce the gene’s effect, respectively.
The altered GDF11 released more propeptides, which diminished the gene’s overall effect. The scientists placed a strand of the altered gene into eggs that developed into mice showing extra bone growth only on one vertebra and higher bone density.
Previous studies had completely turned off GDF11’s function and resulted in mice with extra bone growth all along the spine. They died before birth.
In the foreseeable future, studying the altered mice could help biologists understand the causes of skeletal defects that result in stillborn children and childhood skeletal problems, the paper said. It might lead to treatments for osteoporosis.
Yang said he continues to work on understanding the effect of GDF11 on bone density. Developing a way to decrease GDF11 expression in adults, such as through the use of drugs, could counter osteoporosis and lead to stronger bones, he said.
The research was funded by the U.S. Department of Agriculture and the National Institutes of Health.
