Kurt D. Hankenson, D.V.M., Ph.D., a U-M assistant professor of orthopedic surgery and laboratory animal medicine, and Christina N. Bennett, a U-M graduate student and first author of the PNAS paper, used a technology called micro-computerized tomography to scan femur (leg) bones from mice that inherited the FABP4-Wnt10b gene combination and compare them to scans from normal mice.
Bennett and Hankenson discovered that femurs from the transgenic mice had almost four times as much bone, and were mechanically stronger than femurs from control mice. (Note to editors: An image showing the femur scan comparison is available.)
"It was a very exciting moment the first time we saw scans showing increased bone mass in transgenic mice," Bennett says. "Visually, we don't see any abnormal side-effects in bone from the transgenic mice. Its development and morphology appear to be completely normal."
Loss of bone often develops with aging, but Wnt10b transgenic mice maintained their high levels of bone mass up to the ripe old age of 23 months, when the study was concluded.
Estrogen deficiency in females is another common cause of bone loss. When U-M scientists removed ovaries from normal mice in the study, they developed reduced bone mineral density and bone volume. But the Wnt10b females showed no bone loss after their ovaries were removed. "Because the transgenic mice have more trabecular bone, or bone within the marrow cavity, to begin with, they are doubly protected from the usual loss of bone density due to estrogen deficiency," MacDougald adds.
To confirm that Wnt10b was the key to increased bone formation, Bennett and Hankenson scanned bones from a strain of laboratory mice that didn't have a gene for Wn