Manipulating these tiny splints consistently and accurately was a challenging technical feat, Helms said. "It requires people with great hands," she said, such as Diane Hu, MD, the staff specialist who perfected the technique.

After 10 days of this treatment, x-rays showed that only cartilage and other fibrous cells grew in the gap, or interzone, between the pieces of broken bone.

Helms and her colleagues then injected doses of VEGF into the interzones of 10 broken mouse legs, and made sham injections to 10 others. After ten days of splint-shifting, the researchers could see osteoblasts, or bone growth cells, developing in interzones of the mice injected with VEGF. The sham-injected mice still had only fibrous tissue growth. The VEGF-injected mice also had much higher expression of the gene Cbfa1, which is thought to help stimulate formation of new osteoblasts.

Although more research is necessary, VEGF treatment could help to give a happy ending to the tragic stories of patients who suffer from non-bony healing, said Ted Miclau, MD, an orthopedic surgeon who works in Helms' lab. "The fractures that tend not to heal are open fractures and those from high energy accidents, such as high speed auto, or pedestrian vs. auto accidents,' he said.

In addition to studying VEGF's role in bone healing, Helms' lab is examining whether it might also be important in embryonic bone growth. They have begun injecting either VEGF or inhibitors of VEGF into the limbs of embryonic chickens as they develop in the egg. They will then examine the effects of too little or too much VEGF on skeletal development.

Other researchers collaborating on the project were UCSF orthopaedic surgery residents Mark Lee, MD, and Christian Oglivie, MD, post-doctoral
'"/>

Contact: Kevin Boyd
kboyd@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
12-Mar-2000