Periodontitis is an inflammatory disease of the periodontium and a leading cause of adult tooth loss. Therapy and regeneration present a major challenge to dentistry. Cell biologist Oleh Andrukhov is breaking new ground by studying how dental stem cells interact with the immune system. His data shows that vitamin D3, among other things, 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 useful for humans, the body’s immune system can defend itself from less useful rest. However, if some bacteria take over, a weakened immune system is no longer able to fight the pathogens. This condition can lead to periodontitis, which can lead to chronic inflammation of the periodontium and even tooth loss if left untreated. Thanks to the Vienna researchers, the overall picture of the interaction behind this complicated inflammatory process has now been enriched with a piece of the puzzle.
“We know that so-called dental mesenchymal stem cells (MSCs) play an important role,” says Oleh Andrukhov of the University of Vienna Dental Clinic. “So far we have mainly considered them as a useful tool for tissue regeneration. But they also have the ability to influence immune cells. Therefore they have an immunomodulating effect “. Recent studies have already suggested that MSCs have different immunomodulatory capabilities. However, these differences have never been systematically studied. A team of graduate, graduate and graduate students led by cell biologist Oleh Andrukhov has now taken on this task as part of a five-year project funded by the Australian Science Fund FWF. Furthermore, the group hypothesized that the interaction of dental MSCs with immune cells plays an essential role in periodontitis. They also looked at the influence of vitamin D3 on this interaction. The reason for this: “It has long been assumed that a lack of vitamin D3 is a risk factor for periodontitis.”
For investigations, the research team isolated blood cells from dental and physically healthy test subjects, as well as mesenchymal stem cells (progenitor cells) from extracted (pulled) teeth. “In order to study the interaction between stem and immune cells and vitamin D3, we developed our model,” says Andrukhov, who heads the Competence Center for Periodontal Research at the Dental Clinic of the University of Vienna. Together with his team, the researcher found a perfectly balanced system. “There is a constant bidirectional interaction between immune cells and dental stem cells.” Normally, this interaction is maintained in equilibrium, but in the end it depends on the local conditions of the oral cavity, especially on the presence of inflammatory cytokines (transmitters of immune cells). 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 a reduction in the production of cytokines. A balance of this interaction could be essential 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 various ways. On the one hand, vitamin D3 inhibits the activity of various immune cells and thus reduces the production of pro-inflammatory cytokines. At the same time, vitamin D3 also inhibits the immunomodulatory activity of dental MSCs. These properties of vitamin D3 are in turn inhibited by bacterial factors and regulated by cytokines. Therefore, vitamin D3 affects local conditions, at the same time its bioactivity is modulated by these conditions.
follow-up project started
This suggests that vitamin D3 could be used at higher doses as an adjunct therapy for periodontitis and, again, the effectiveness of vitamin D3 could be improved by changing the local setting. “However, optimal conditions have yet to be sought,” says Andrukhov. In any case, the results open a new perspective for future research projects. “In a follow-up project, we are now investigating which stem cell subpopulation is best suited for therapeutic use. This allows us to bridge the gap between basic research and clinical application.” the scientist’s term is to create and further develop his 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 finding solutions to the challenge of dentistry “.
Blufstein A., Behm C., Kubin B., Gahn J., Moritz A., Rausch-Fan X., Andrukhov O .: Effect of vitamin D.3 on the osteogenic differentiation of stromal cells of the human periodontal ligament 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 on CD4+ Human Periodontal Ligament Cell Mediated T Lymphocytes and 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 Tissue-Derived Mesenchymal Stem Cells: Implication in Disease and Tissue Regeneration, in: World Journal of Stem Cells 2019
Source: University Dental Clinic Vienna, Austrian Science Fund FWF