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Gum disease and arthritis: How bacteria in your mouth could be hurting your joints

ANI | | Posted by Akanksha Agnihotri, Tokyo
Sep 09, 2024 04:17 PM IST

Research indicates that infection with A. actinomycetemcomitans worsens rheumatoid arthritis symptoms in mice by triggering inflammatory responses.

Periodontal disease, which affects the gums and tissues around the teeth, is one of the most common dental disorders globally. Periodontal disease, which is most commonly caused by the growth and deposition of bacterial biofilm around the teeth, can eventually lead to tooth loss if not treated properly.

Research links periodontal disease to worsening rheumatoid arthritis symptoms(Shutterstock)
Research links periodontal disease to worsening rheumatoid arthritis symptoms(Shutterstock)

Periodontal disease, which is most commonly caused by the growth and deposition of bacterial biofilm around the teeth, can eventually lead to tooth loss if not treated properly. Interestingly, the inflammatory effects of periodontal bacteria can extend well beyond the mouth, resulting in systemic consequences. Several decades of clinical research have proven that the periodontal pathogen Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is closely related to the onset and worsening of rheumatoid arthritis (RA), a serious autoimmune disease that affects joints. However, what goes down at the molecular level remains largely unexplored and unclear.

How Gum Disease May Worsen Arthritis

In a recent study published online on 15 August 2024, in the International Journal of Oral Science, a research team from Tokyo Medical and Dental University (TMDU) in Japan sought to fill this knowledge gap through detailed mechanistic studies in an animal model.

First, the researchers conducted preliminary experiments to confirm whether A. actinomycetemcomitans infection influenced arthritis in mice. To this end, they used the collagen antibody-induced arthritis mouse model, which is a well-established experimental model that mimics several aspects of RA in humans. They found that infection with this specific bacterium led to increased limb swelling, cellular infiltration into the lining of the joints, and higher levels of the inflammatory cytokine interleukin-1b (IL-1b) within the limbs.

Notably, these symptoms of increasing RA can be alleviated by injecting clodronate, a chemical substance that depletes macrophages, a type of immune cell. This showed that macrophages were implicated in exacerbating RA induced by A actinomycetemcomitans infection. Further investigation using macrophages derived from mouse bone marrow revealed that A. actinomycetemcomitans infection increased the production of IL-1b. 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.

The researchers added yet one more piece to this puzzle using 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. "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," highlights Professor Toshihiko Suzuki, one of the lead authors of the study.

With any luck, these efforts will contribute to the development of novel therapeutic strategies to manage RA. "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," says lead author Dr Tokuju Okano. "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," he adds with eyes set on the future.

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