Abnormal bone remodelling activity of dental follicle cells from a cleidocranial dysplasia patient.
Кључне речи
Апстрактан
OBJECTIVE
To explore the role of dental follicle cells (DFCs) with a novel cleidocranial dysplasia (CCD) causative gene RUNX2 mutation (DFCsRUNX2+/m ) in delayed permanent tooth eruption.
METHODS
A CCD patient with typical clinical features was involved in this study. DFCsRUNX2+/m were cultured and DNA was extracted for RUNX2 mutation screening. Measurements of cell proliferation, alkaline phosphatase (ALP) activity, alizarin red staining and osteoblast-specific genes expression were performed to assess osteogenesis of DFCsRUNX2+/m . Co-culture of DFCs and peripheral blood mononuclear cells (PBMCs), followed tartrate-resistant acid phosphatase (TRAP) staining, real-time PCR and western blot were performed to evaluate osteoclast-inductive capacity of DFCsRUNX2+/m .
RESULTS
A missense RUNX2 mutation (c. 557G>C) was found in DFCsRUNX2+/m from the CCD patient. Compared with normal controls, this mutation did not affect the proliferation of DFCsRUNX2+/m , but down-regulated the expression of osteogenesis-related genes, leading to a decrease in ALP activity and mineralisation. Co-culture results showed that DFCsRUNX2+/m reduced the formation of TRAP+ multinucleated cells and the expression of osteoclastogenesis-associated genes. Furthermore, the mutation reduced the ratio of RANKL/OPG in DFCsRUNX2+/m .
CONCLUSIONS
DFCsRUNX2+/m disturbs bone remodelling activity during tooth eruption through RANK/RANKL/OPG signalling pathway and may thus be responsible for impaired permanent tooth eruption in CCD patients.
