Rheumatoid Arthritis Linked to Periodontal Disease
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- Published: Thursday, 12 September 2024 16:09
- Written by Peter Ingle
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The association between oral health and general health is now well established. In particular it is now accepted that our patients with periodontal disease may be fast tracking themselves for other conditions such as type 2 diabetes. Chronic heart and kidney disease are also linked and there are increasing numbers of studies showing an association with dementia.
While demonstrating an association does not in itself confirm causality, there is a suggestion that the chronic inflammatory nature of periodontal disease may be a key factor.
Recent research suggests that there is another serious condition to add to the list.
There had been clinical studies showing that the periodontal pathogen Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is related to the onset and worsening of rheumatoid arthritis (RA). In a recent study published in International Journal of Oral Science, a research team from Tokyo Medical and Dental University (TMDU) sought to fill this knowledge gap through detailed studies in an animal model.
Initially the researchers conducted preliminary experiments to confirm whether A. actinomycetemcomitans infection influenced arthritis in mice. They used an existing arthritis mouse model, which 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 inflammatory cytokines within the limbs.
Notably, these symptoms of worsening RA could be suppressed by administering a chemical agent, clodronate that depletes macrophages. 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 the inflammatory cytokines found within the limbs. In turn, this triggered the activation of an inflammasome, which plays a key role in initiating and modulating the body’s inflammatory response to infections. Inflammasomes are multiprotein complexes within the immune system responsible for the activation of inflammatory responses and cell death.
The researchers added another piece to the puzzle using caspase-11-deficient mice. Mouse caspase-11, and the similar human caspase-4 and caspase-5, are intracellular receptors that are involved during the immune response. 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," said Professor Toshihiko Suzuki, one of the lead authors of the study.
It is hoped that this knowledge 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," said lead author Dr. Tokuju Okano.
That might just be the start, given the other conditions associated with periodontal disease. According to Dr 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.".
Image Credit: Bernd Brägelmann Braegel Mit freundlicher Genehmigung von Dr. Martin Steinhoff, CC BY 3.0, via Wikimedia Commons
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