Periodontal disease affects the gums and tissues that surround the teeth and is one of the most prevalent dental conditions in the world. According to the National Institute for Health and Care Excellence (NICE), almost half of UK adults have a degree of periodontitis that is irreversible.

Periodontal disease, often caused by the formation and accumulation of bacterial biofilm around the teeth, can lead to tooth loss if left unattended. According to researchers, the inflammatory effects of periodontal bacteria can go well beyond the mouth, leading to systemic effects.

Previous studies have revealed that the periodontal pathogen Aggregatibacter actinomycetemcomitans is closely related to the onset and worsening of rheumatoid arthritis (RA), a serious autoimmune disease that affects joints.

The latest research

In a study published in August 2024 in the International Journal of Oral Science, a research team from Tokyo Medical and Dental University (TMDU) explored this on a molecular through detailed mechanistic studies in an animal model.

The researchers conducted preliminary experiments to confirm whether A. actinomycetemcomitans infection influenced arthritis in mice. They used the collagen antibody-induced arthritis mouse model, a well-established experimental model that mimics several aspects of RA in humans.

Researchers found that infection with this specific bacterium led to increased limb swelling, cellular infiltration into the joint lining, and higher levels of the inflammatory cytokine interleukin-1β (IL-1β) within the limbs.

These symptoms of worsening RA could be suppressed by administering clodronate, a chemical agent that depletes macrophages—a type of immune cell. This demonstrated that macrophages were somehow involved in aggravating RA caused by A. actinomycetemcomitans infection.

Further investigation using macrophages derived from mouse bone marrow revealed that A. actinomycetemcomitans infection increased the production of IL-1β. In turn, this triggered the activation of a multiprotein complex known as the inflammasome, which plays a key role in initiating and modulating the body’s inflammatory response to infections.

Toshihiko Suzuki, one of the lead authors, said, “Our research findings provide new insights into the link between periodontal pathogenic bacteria and the exacerbation of arthritis through inflammasome activation, offering important information on the long-debated relationship between periodontal disease and systemic diseases”.

To further their research, they also used caspase-11-deficient mice. In these animals, inflammasome activation due to A. actinomycetemcomitans was suppressed. Most importantly, caspase-11-deficient mice exhibited less deterioration of arthritis symptoms, hinting at the important role that caspase-11 plays in this context.

The researchers hope their efforts will contribute to developing novel therapeutic strategies to manage RA.

Tokuju Okano, the lead author, said, “The findings of this research may pave the way for advances in clinical treatments for RA induced by infection with A. actinomycetemcomitans. Our suggestion to inhibit inflammasome activation could attenuate the expansion of inflammation to joints, resulting in a recovery from arthritis symptoms.

“Moreover, the outcome of our work could contribute to the development of treatment strategies for not only arthritis but also other systemic diseases, such as Alzheimer's disease, which is also related to periodontal pathogenic bacteria.”

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