Local vitamin D₃ bioactivation in oral tissue, from inactive to influential: A narrative review

Vitamin D₃ status profoundly affects oral health and disease. Over the last decade, evidence has emerged that vitamin D₃ activation can also occur in peripheral tissues. This narrative review was conducted to critically analyze the state of the art about the presence and activity of enzymes involved in the bioactivation of vitamin D₃ in the oral tissues.

A comprehensive literature search was performed in PubMed and Google Scholar. The search included articles published in English without any time limit. Keywords included but not limited to the combinations of: "vitamin D₃", "25(OH)D₃", "1,25(OH)₂D₃", "oral tissues", "megalin", "CYP27B1", "extrarenal", and "antimicrobial peptides". Further studies were identified by screening the reference lists of the relevant publications.

Various vitamin D₃ metabolites influence the inflammatory response and the production of antimicrobial peptides in various oral cells. The enzyme CYP27B1, which is responsible for the conversion of 25(OH)D₃ into 1,25(OH)₂D₃ and its bioactivation, is present in various oral tissues and cells. The existence and physiological significance of local vitamin D₃ activation in oral tissues remain unclear. Most of 25(OH)D₃ is bound to the vitamin D-binding protein (DBP) and must be dissociated for activation. It is unclear whether and how this uncoupling occurs in oral tissue.

Currently, there is rather indirect evidence that vitamin D₃ could be bioactivated in oral tissues. Further studies on the local conversion of vitamin D₃ to 25(OH)D₃ and, subsequently, to 1,25(OH)₂D₃ in oral tissue, their regulation, and the role of free and bioavailable vitamin D₃ metabolites are required.