Discovery Hints At the Immune System's Role in Bone Loss
Researchers have known of the relationship between high cholesterol and osteoporosis, but understanding the mechanism behind the connection has eluded them. Lead author, Rita Effros, suspected that fatty acid oxidation (cell and tissue damage from free radical exposure) was involved.
In the study, researchers examined LDL or “bad” cholesterol and its affect on bones. They were looking for whether a specific immune cell known as a T cell plays a role in the process. The researchers found that half of the T cells were combined with normal LDL – and the rest were combined with oxidized LDL. The scientists then stimulated half of the T cells to mimic an immune response and left the rest alone.
Effros’ response was clear, “Lo and Behold, both the resting and the activated T cells started churning out a chemical that stimulates cells whose sole purpose is to destroy bone.” Known as RANKL, this chemical is involved in immune response and bone physiology.
To investigate this process further, researchers examined mice fed a high-fat diet as well as a control group fed a normal diet. After 11 months, the mice on the high-fat diet had elevated cholesterol levels and thinner bones. When the researchers tested the T cells of the high cholesterol mice, they found the cells switched on the gene that produces RANKL.
Effros concludes, “It’s normal for our T cells to produce small amounts of RANKL during an immune response. 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. The animals’ high cholesterol increased their levels of oxidized LDL, which told the T cells to keep generating RANKL.”
The next step will be exploring how to control T cell responses to oxidized LDL in an effort to develop immune-based approaches to preventing or slowing bone loss.
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