Vitamin D3 metabolism in dental MSCs

Mesenchymal stem/stromal cells (MSCs) are a promising instrument in regenerative medicine, particularly dentistry. The effectiveness of MSCs was shown in different experimental disease models and is currently tested in various clinical settings. The advantage of these cells is their availability and the absence of ethical issues in their isolation and applications. Within the last years, MSCs have been found in numerous dental tissues. This fact attracted the attention of researchers and clinicians because MSCs could be isolated from the extracted teeth, representing a "medical waste". Vitamin D3 is an important hormone that regulates several critical physiological processes in the body. Although the human body can produce some amounts of vitamin D3, this is usually insufficient, and therefore, additional supplementation via nutrients is required. Vitamin D 3 deficiency is associated with several systemic diseases, including cardiovascular diseases and diabetes, as well as oral diseases, particularly periodontitis. Our recent research has shown that vitamin D3 also influences various properties of dental MSCs. In the present project, we will continue investigating the versatile effects of vitamin D3 in dental tissues. Several aspects will be examined in detail. The first point to be studied is the possibility of vitamin D 3 conversion, activation, and inactivation in dental MSCs. Vitamin D3, which is produced by the skin or obtained as a nutrient, is further converted by various enzymes in the liver and kidney into different metabolites with various biological activities. We will investigate if and how dental MSCs might convert and activate vitamin D 3 and produce various vitamin D 3 metabolites. The regulation of these processes by various physiological factors, such as ions, hormones, and growth factors, will be investigated. Furthermore, the activity of various vitamin D3 metabolites in dental MSCs will be examined. The second part of this project will be focused on the immunomodulatory activities of dental MSCs. As shown by previous studies, MSCs modulate the function of several types of immune cells, and this effect is responsible not only for their regenerative potential but also for maintaining homeostasis in different tissues. We have already shown that vitamin D3 affects the immunomodulatory function of dental MSCs. In the present project, we will continue to investigate the interplay between vitamin D 3 conversion by dental MSCs and their immunomodulatory function. Finally, we will attempt to translate our findings into the clinical situation. In particular, we will investigate periodontal tissue samples from healthy and periodontitis patients and compare the expression of different proteins involved in vitamin D3 activation. Summarizing this project will be helpful in clarifying the mechanisms of vitamin D 3 effects in dental tissues and the necessity of vitamin D3 supplementation in oral health maintenance and periodontal therapy.