Half the animals were fed a high-fat diet starting at one month of age, while the control group ate a normal diet. At 11 months, the mice on the high-fat diet showed elevated cholesterol and thinner bones.

When Effros and her colleagues tested the T cells of the mice on the high-fat diet, they discovered that the cells acted differently than those of the mice on the normal diet.

The T cells switched on the gene that produces RANKL. The chemical also appeared in the animals' bloodstream, suggesting that the cellular activity contributed to their bone loss.

"It's normal for our T cells to produce small amounts of RANKL during an immune response," explained Effros. "But when RANKL is manufactured for long periods or at the wrong time, it results in excessive bone damage."

"That's exactly what happened to the mice on the high-fat diet," she said. "The animals' high cholesterol increased their levels of oxidized LDL, which told the T cells to keep generating RANKL. This discovery revealed to us how the immune system might play an entirely new role in bone loss."

The next step will be exploring methods to control T cell response to oxidized LDL in an effort to develop immune-based approaches to prevent or slow bone loss, Effros says.

Source: University of California - Los Angeles