Multiple effects of dose-related GM-CSF on periodontal resorption in deep-frozen grafted teeth: A reverse study

Autologous tooth grafting is a dental restorative modality based on periodontal ligament healing. Human periodontal ligament stem cells (PDLSCs) are involved in the formation and remodeling of periodontal tissue. Based on previous findings, the proliferation and differentiation of processing cryopreserved periodontal ligament stem cells (PDLSCs) exhibit similarities to those of fresh cells. However, there is evident absorption in the transplanted frozen tooth's roots and bones, with the underlying cause remaining unknown. Granulocyte macrophage colony-stimulating factor (GM-CSF) is named for its produce granulocyte and macrophage precursors from bone marrow precursors, and it also serves as one of the regulatory factors in inflammatory and osteoclast formation. This study aimed to investigate changes in GM-CSF expression in frozen PDLSCs (fhPDLSCs) and evaluate the impact of GM-CSF on PDLSCs with respect to cellular activity and osteogenic ability. The role of GM-CSF in periodontal absorption was further speculated by comparing with IL-1β. The results revealed a significant increase in GM-CSF levels from fhPDLSCs compared to fresh cells, which exhibited an equivalent inflammatory stimulation effect as 1 ng/ml IL-1β. Cell viability also increased with increasing concentrations of GM-CSF; however, the GM-CSF from fhPDLSCs was not sufficient to significantly trigger osteoclastic factors. Considering its interaction with IL-1β and positive feedback mechanism, environments with high doses of GM-CSF derived from fhPDLSCs are more likely to activate osteoclastic responses. Therefore, for frozen tooth replantation, great attention should be paid to anti-inflammation and anti-infection. GM-CSF may serve as a potential therapeutic target for inhibiting periodontal resorption in delayed grafts.