RUNX2 mutation inhibits the cellular senescence of dental follicle cells via ERK signalling pathway

Abstract

ObjectiveThe aim of this study was to explore the regulatory effect of RUNX2 mutation on dental follicle cells (DFCs) senescence and clarify the underlying mechanism. This study aimed to explore the basis for a novel mechanism of delayed permanent tooth eruption in cleidocranial dysplasia (CCD) patients.Materials and MethodsDental follicles were collected from a CCD patient and healthy controls. Senescence‐associated β‐galactosidase (SA‐β‐gal) staining, Ki67 staining, cell cycle assays, and senescence‐related gene and protein expression assays were performed to assess DFCs senescence. Western blotting was performed to detect the activation of mitogen‐activated protein kinase (MAPK) signalling pathways, and the molecular mechanism underlying RUNX2 regulating in DFCs senescence was explored.ResultsRUNX2 mutation inhibited the cellular senescence of DFCs from the CCD patient compared with healthy controls. Ki67 staining showed that mutant RUNX2 promoted DFCs proliferation, and cell cycle assays revealed that the healthy control‐derived DFCs arrested at G1 phase. RUNX2 mutation significantly downregulated senescence‐associated gene and protein expression. RUNX2 mutation suppressed ERK signalling pathway activation, an ERK inhibitor decreased healthy control‐derived DFCs senescence, and an ERK activator promoted CCD patient‐derived DFCs senescence.ConclusionsRUNX2 mutation delayed DFCs senescence through the ERK signalling pathway, which may be responsible for delayed permanent tooth eruption in CCD patients.

Spatiotemporal cellular dynamics and molecular regulation of tooth root ontogeny

“…Therefore, the presence of the Runx2 mutation in CCD prevents the cellular senescence process of DFSCs by blocking the ERK signaling pathway. 122 Activated Notch1 signaling pathway was required in the osteogenic differentiation of DFSCs. Activation of the NOTCH1 inhibited osteogenic differentiation via BMP2/DLX3 pathway in DFSCs.…”