Periodontal disease, which affects the gums and tissues around the teeth, is one of the most common dental disorders worldwide. Periodontal disease, which is usually caused by the growth and deposition of bacterial biofilm around the teeth, can eventually lead to tooth loss if not properly treated.
Periodontal disease, which is usually caused by the growth and deposition of bacterial biofilm around the teeth, can eventually lead to tooth loss if not properly treated. Interestingly, the inflammatory effects of periodontal bacteria can extend far beyond the mouth, resulting in systemic consequences. Several decades of clinical research have demonstrated that the periodontal pathogen Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is closely associated with the onset and exacerbation of rheumatoid arthritis (RA), a severe autoimmune disease affecting the joints. However, what goes down at the molecular level remains largely unexplored and unclear.
How gum disease can make arthritis worse
In a recent study published online August 15, 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 affected arthritis in mice. To this end, they used the collagen antibody-induced murine arthritis model, which is a well-established experimental model that mimics many aspects of RA in humans. They found that infection with this particular bacterium led to increased limb swelling, cellular infiltration into the joint lining, and higher levels of the inflammatory cytokine interleukin-1b (IL-1b) within the limbs.
Specifically, these symptoms of increasing rheumatoid arthritis can be alleviated by injecting clodronate, a chemical that depletes macrophages, a type of immune cell. This indicated that macrophages are involved in the exacerbation of RA caused by A actinomycetemcomitans infection. Further investigation using mouse bone marrow-derived macrophages revealed that A. actinomycetemcomitans infection increased IL-1b production. In turn, this triggered the activation of a multiprotein complex known as the inflammasome, which plays a key role in initiating and regulating the body’s inflammatory response to infection.
The researchers added another piece to this puzzle using caspase-11-deficient mice. In these animals, activation of the inflammasome due to A actinomycetemcomitans is suppressed. More importantly, caspase-11-deficient mice showed less worsening of arthritis symptoms, implying the important role that caspase-11 plays in this context. “The findings of our research provide new insights into the relationship between periodontal pathogenic bacteria and the exacerbation of arthritis through the activation of inflammasomes, offering important insights into the long-term relationship between periodontal disease and systemic diseases,” points out Professor Toshihiko Suzuki, one of the main authors. of the study.
With any luck, these efforts will contribute to the development of new therapeutic strategies for the management of RA. “The findings of this research may pave the way for advances in clinical treatments for RA caused by A. actinomycetemcomitans infection. Our proposal to inhibit inflammasome activation could moderate the spread of inflammation in joints, with result in recovery from arthritis symptoms,” he says. lead author Dr Tokuju Okano; “Furthermore, the result of our work could contribute to the development of treatment strategies not only for arthritis but also for other systemic diseases, such as Alzheimer’s disease, which is also associated with periodontal pathogenic bacteria,” he adds, looking to the future. .
