Periodontitis is an inflammatory disease of the periodontium and the main cause of tooth loss in adulthood. Therapy and regeneration represent a great challenge for dentistry. Cell biologist Oleh Andrukhov has gone through a new path by examining how dental stem cells interact with the immune system. His data show that vitamin D3, among others, plays a crucial role.
As an entry point into the body, the oral cavity is inhabited by a particularly large number of different bacteria. Most of them are beneficial for humans, the body’s own immune system can defend itself against less helpful rest. However, if certain bacteria gain the upper hand, a weakened immune system is no longer able to fight the pathogens. This condition can lead to periodontitis, which, if left untreated, can lead to chronic periodontal inflammation and even tooth loss. Thanks to scientists from Vienna, the overall picture of the interaction that underlies this complicated inflammatory process has now been enriched with a jigsaw puzzle.
A new perspective
“We know that so-called dental mesenchymal stem cells (MSCs) play an important role,” says Oleh Andrukhov of the University Dental Clinic in Vienna. “Until now, we have considered them mainly as a useful tool for tissue regeneration. But they also have the ability to affect immune cells. Thus, they have an immunomodulatory effect. ”Recent studies have suggested that MSCs have different immunomodulatory abilities. However, these differences have never been systematically studied. A team of postdoctoral, doctoral and master’s students led by the cell biologist Oleh Andrukhov has now taken on this task as part of a five-year project funded by the Austrian Science Fund FWF. In addition, the group hypothesized that the interaction of dental MSCs with immune cells plays a crucial role in periodontitis. They also investigated the effect of vitamin D3 on this interaction. The reason: “Vitamin D3 deficiency has long been thought to be a risk factor for periodontitis.”
For the purposes of the investigation, the research group isolated blood cells from dentally and physically healthy test subjects as well as mesenchymal stem cells (progenitor cells) from extracted (ripped) teeth. “To be able to investigate the interaction between stem and immune cells and vitamin D3, we have developed our own model,” says Andrukhov, who heads the periodontal research competence center at Vienna’s University Dental Clinic. Together with his team, the researcher found a perfectly balanced system. “There is a constant, two-way interaction between immune cells and dental stem cells.” Normally, this interaction is kept in balance, but ultimately depends on local conditions in the oral cavity, especially the presence of inflammatory cytokines (immune cell transporters). On the one hand, the production of cytokines by immune cells activates dental MSCs. On the other hand, dental MSCs suppress the activity of immune cells, resulting in lower cytokine production. A balance of this interaction may be necessary for the progression of periodontitis and for the regeneration of dental tissues.
Influence of vitamin D3
The data also showed that this balanced interaction between immune cells and dental MSCs is affected by vitamin D3 in a variety of ways. On the one hand, vitamin D3 inhibits the activity of various immune cells and thus reduces the production of proinflammatory cytokines. At the same time, vitamin D3 also inhibits the immunomodulatory activity of dental MSCs. These properties of vitamin D3, in turn, are inhibited by bacterial factors and regulated by cytokines. Vitamin D3 therefore affects local conditions, at the same time its bioactivity is modulated by these conditions.
follow-up project began
This suggests that vitamin D3 could be used at higher doses as an adjunctive treatment for periodontitis, and again, the effectiveness of vitamin D3 could be improved by changing the locale. “However, optimal conditions have yet to be explored,” says Andrukhov. In any case, the results open up a new perspective for future research projects. “In a follow-up project, we are now investigating which stem cell subpopulation is most suitable for therapeutic use. This allows us to bridge the gap between basic research and clinical application. ”The researcher’s long-term goal is to establish and further develop its own research group. “The whole picture of how everything develops in the mouth is very complicated and at the same time very elegant. I really enjoy doing research in this area and looking for solutions to the challenges of dentistry. ”
Blufstein A., Behm C., Kubin B., Gahn J., Moritz A., Rausch-Fan X., Andrukhov O .: Effect of vitamin D.3 on osteogenic differentiation of stromal cells of human periodontal ligaments in inflammatory conditions, in: Journal of Periodontal Research 2021
Behm C., Blufstein A., Gahn J., Kubin B., Moritz A., Rausch-Fan X., Andrukhov O .: Pleiotropic effects of vitamin D.3 and CD4+ T lymphocytes mediated by human periodontal fibrous cells and the inflammatory environment, in: Journal of Clinical Periodontology 2020
Behm C., Blufstein A., Gahn J., Nemec M., Moritz A., Rausch-Fan X., Andrukhov O .: Cytokines differently define the immunomodulation of mesenchymal stem cells from the periodontal ligament, in: Cells 2020
Andrukhov O., Behm C., Blufstein A., Rausch-Fan X .: Immunomodulatory Properties of Mesenchymal Stem Cells Derived from Dental Tissue: Implications for Disease and Tissue Regeneration, in: World Journal of Stem Cells 2019
Source: University Dental Clinic Vienna, Austrian Science Fund FWF