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New Strategy Could Thwart Periodontal Disease Progress

By BiotechDaily International staff writers
Posted on 02 Jan 2013
A new study suggests that blocking a specific molecular receptor on white blood cells (WBCs) could prevent periodontitis from developing, as well as halting the progression of the disease once it has already developed.

Researchers at the University of Pennsylvania (Penn, Philadelphia, USA) showed (in a mouse model) that Porphyromonas gingivalis--the bacterium responsible for many cases of periodontitis--acts by “hijacking” a receptor on WBCs called C5aR, which is part of the complement system, a component of the immune system that helps clear infection but can trigger damaging inflammation if improperly controlled. By hijacking C5aR, P. gingivalis subverts the complement system and handicaps immune cells, rendering them less able to clear infection from the gum tissue, resulting in severe inflammation.

Other studies have shown that toll-like receptors (TLRs, a set of proteins that also activate immune cell responses) may also act in concert with the complement system; in fact, mice that are C5aR-deficient and those lacking TLR2 do not develop bone loss. The researchers therefore tried to determine if the synergism seen between the complement system and TLRs was also at play in inflammatory gum disease. To find out, they injected two types of molecules, one that activated C5aR and another that activated TLR2, into the gums of mice. When only one type of molecule was administered, a moderate inflammatory response became apparent, but when injected together, inflammatory molecules increased dramatically.

In fact, the inflammatory molecules soared to levels higher than would have been expected if the effect of activating both receptors was merely additive. The finding suggested to the scientists that the TLR signaling was somehow involved in "crosstalk" with the complement system, serving to augment the inflammatory response. They then surmised that blocking one of the receptors could effectively halt the inflammation that allows P. gingivalis and other bacteria to thrive and cause disease.

To test the hypothesis, the researchers synthesized and administered a molecule that blocks the activity of C5aR to mice that were then infected with P. gingivalis. Subsequent C5aR antagonist injections were able to stave off inflammation to a large extent, reducing inflammatory molecules by 80% and completely stopping bone loss. Similar effects were seen when the mice were given the antagonist two weeks after being infected, reducing signs of inflammation by 70% and inhibiting nearly 70% of periodontal bone loss. The study was published in the Journal of Immunology.

“Regardless of whether we administered the C5a receptor antagonist before the development of the disease or after it was already in progress, our results showed that we could inhibit the disease either in a preventive or a therapeutic mode,” said senior author Professor George Hajishengallis, DDS, PhD.

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