Feature Story

Health Center Today, August 31, 2009

New Insights into Limb Formation

By Carolyn Pennington

Robert Kosher

Health Center researchers working with investigators at Burnham Institute for Medical Research in San Diego have gained new understanding of the role hyaluronic acid (HA) plays in skeletal growth, chondrocyte maturation and joint formation in developing limbs. Robert Kosher, a professor in the Center for Regenerative Medicine and Skeletal Development, says the findings are a breakthrough in this field of research.

HA is a large sugar molecule that is produced by every cell in the body and has been thought to play a role in joint disease, heart disease and invasive cancers.  Because hyaluronic acid is so prevalent in the body, it has been difficult to study. 

For this study, scientists used a novel mouse model in which the production of HA is blocked in a tissue-specific manner. The researchers then genetically modified the Has2 gene - a critical enzyme for HA synthesis - so that the gene could be "conditionally" disrupted in mice. They showed that the mice, in which Has2 was inactivated in the limb bud mesoderm, had shortened limbs, abnormal growth plates and duplicated bones in the fingers and toes.  Kosher says this is the first time this mouse model has been created, and it will be extremely useful in studying the role of HA in various age-related diseases and conditions such as arthritis and skin aging, as well as cancer.

The study, funded by grants from the National Institutes of Health, is published online in the journal Development.