Effect of vitamins A/C primed human gingival mesenchymal stem/progenitor cells in preventing medication-related osteonecrosis of extraction socket: an animal study

Human gingival mesenchymal stem/progenitor cells (hGMSCs) exert remarkable tissue regeneration properties. A combination of vitamins C and A at specified concentrations enhanced cellular dedifferentiation and multipotency of hGMSCs. To our knowledge, vitamins A/C-primed hGMSCs in the prevention of medication-related osteonecrosis of the jaw (MRONJ) have not been investigated. Thus, this study evaluated the impact of vitamins A/C in pluripotency-inductive concentrations on the regenerative/reparative potential of hGMSCs in preventing MRONJ development in rats. Thirty albino rats (n = 10/group) were administered zoledronic acid and dexamethasone three times a week for 4 weeks. The upper first molar was extracted 2 weeks following the first administration. Immediately after extraction, rats received normal saline (group Ι), hGMSCs (group ΙΙ), and hGMSCs primed with vitamins A/C (group ΙΙΙ). Rats were euthanized 2 and 4 weeks after extraction. The maxillae were analyzed using dual-energy X-ray absorptiometry, histologically, histomorphometrically, and by quantitative real-time polymerase chain reaction analysis. Groups II and III displayed elevated bone mineral density, with a significant rise in group ΙΙΙ relative to group ΙΙ at 4 weeks. Histomorphometrically, groups II and III revealed an elevation in area percentage of newly generated bone, with a significant rise in group ΙΙΙ at both time intervals. Gene expression of transforming growth factor-β1 (TGF-β1) and runt-related transcription factor 2 (Runx2) presented a significant elevation in groups II and III, with a significant rise in group ΙΙΙ at both time intervals. In conclusion, vitamins A/C-primed hGMSCs at the tested pluripotency-inductive concentrations prevented MRONJ development, primarily through encouraging wound healing and bone repair in the extraction sockets of rats.