| Dental prosthetic treatment plays a vital role in achieving the mechanical and oral functional restoration.Tooth loss is often caused by oral chronic infectious diseases,which is characterized by the inflammation and destruction of periodontal supporting tissues.Patients who accept dental implantation treatment usually undergo alveolar bone resorption.The ultimate treatment goal is not only to achieve the mechanical repairment but also to reconstruct the damaged periodontal tissue and complete the bioremediation.The DFSCs(Dental Follicle Stem Cells)can differentiate into various periodontal supporting tissues and show excellent osteogenic potential.It has been regarded as the promising seed cell in periodontal tissue regeneration engineering.The regulation on transcriptional elongation plays a key role in cell differentiation processes.As a member of AFF(AF4/FMR2)family,AFF4 is a transcription elongation factor in the SEC(Super Elongation Complex).AFF4 serves as a scaffolding protein to connect other transcription factors and accommodates gene transcription through elongation and chromatin remodeling.Here,we investigated the effect of AFF4 on human DFSCs in osteogenic differentiation.In this study,we found that small interfering RNA-mediated depletion of AFF4 resulted in decreased ALP(Alkaline Phosphatase)activity and impaired mineralization.In addition,the expressions of osteogenic-related genes,such as DLX5,SP7,RUNX2 and BGLAP,were significantly down-regulated.On the contrary,overexpression of AFF4 significantly enhanced the osteogenic potential of human DFSCs.Mechanistically,we found both the m RNA and protein levels of ALKBH1,a critical regulator of epigenetics,changed accordingly with AFF4 expression levels.Overexpression of ALKBH1 in AFF4-depleted DFSCs partially rescued the impairment of osteogenic differentiation.Our data indicated that AFF4 promoted the osteogenic differentiation of DFSCs through up-regulating the transcription of ALKBH1. |
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