New type of gel inhibits periodontal disease – receptor blockade in the oral mucosa prevents inflammation and bone loss

Against gingivitis: US researchers may have found a new, effective remedy for periodontitis. The gel they developed blocks a specific receptor in the oral mucosa and thereby stops the inflammatory processes. In tests, applying this gel to mice prevented inflammation and bone loss, and also inhibited the growth of periodontitis-promoting oral bacteria, the team reports.

Periodontal disease, technically parodontitis, is a widespread disease: almost half of all people develop gingivitis over time. If it persists, such periodontitis can, in extreme cases, even lead to atrophy of the jawbone and tooth loss. Chronic gingivitis is also suspected Cancercardiovascular diseases and even Alzheimer to promote.

Periodontitis leads to inflammation of the gums and degradation of the jawbone. In extreme cases, this can cause teeth to fall out. © TefiM/ GettyImages

The problem: In stubborn cases of periodontitis, even antibiotics and good oral hygiene can only temporarily contain the inflammation. “So far, there is no treatment that inhibits the inflammation and bone loss and also normalizes the disturbed oral flora,” says lead author Yuqi Guo from New York University.

Succinate as an anti-inflammatory

But that could change in the future. Because Guo and his team have discovered a new approach to stubborn periodontitis. The starting point was the observation that periodontosis patients often show significantly increased levels of succinate in their periodontal pockets. This metabolite is released from both the gum tissue and the oral flora and is suspected of promoting gingivitis and pathological imbalances in the oral flora.

Guo and his team therefore first investigated in cell cultures and mice which physiological reactions the succinate triggers. They discovered that a specific receptor on the cells of the oral mucosa plays a crucial role: If they deactivated this docking point, called SUCNR1, by means of a gene blockade, the mice did not develop bone loss despite the same high succinate levels, and the gingivitis was also less severe.

Receptor blockade inhibits periodontitis

This was also confirmed in another test: If the researchers also administered succinate to their mice, the periodontal disease in the control mice worsened. In the animals with the blocked succinate receptor, on the other hand, there were no negative effects: “The SUCNR1-KO mice were resistant to the succinate administration and showed just as little bone loss as healthy control animals,” report Guo and his team.

The oral flora also remained “more normal” in these mice: while pathogenic bacteria from the groups of Bacteroidetes and Saccharibacteria are more common in stubborn periodontitis, this was not the case in the mice with the succinate receptor blockade. “These results strongly suggest that activation of the succinate receptor promotes the manifestation of periodontitis,” the researchers state. “Blocking SUCNR1, on the other hand, significantly reduces susceptibility to periodontitis.”

gel
The transparent gel in these vessels contains a new type of active ingredient against periodontitis. © Yuqi Guo

Active ingredient gel with a triple positive effect

Based on these findings, the scientists have developed a gel that can be easily applied to the gums and whose active ingredient also blocks the succinate receptor. In tests with mice and cultures of human cells, this gel also proved to be effective: mice that received this gel every other day developed significantly less local and systemic inflammation and bone loss in the jaw was also significantly reduced.

Similar to the gene blockade of the succinate receptor, the inhibitor gel also had a positive effect on the oral flora: the proportion of pathogenic and inflammatory Bacteroidetes microbes fell sharply within a few days. “The gel changes the microbial community by regulating inflammation,” explains Guo’s colleague Deepak Saxena.

Hope for new periodontitis therapy

According to the research team, their active ingredient gel opens up a promising opportunity to fight stubborn periodontitis more effectively than before. “The blockade of the succinate receptor by this new agent has clear therapeutic value in combating gingivitis in a more targeted and simple manner than before,” says co-first author Xin Li from New York University.

The scientists are now planning further tests on animals to find out the best dosage and treatment intervals. Her long-term goal is to optimize the gel so that everyone can use it at home in a weaker form. Dentists could introduce a stronger dosage form into the periodontal pockets in cases of severe periodontitis. However, it will still be some time before that happens. (Cell Reports, 2022; doi: 10.1016/j.celrep.2022.111389)

Source: NYU

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