AFF4 regulates osteogenic differentiation of human dental follicle cells.
Qingyue XiaoYuning ZhangXingying QiYaqian ChenRui ShengRuoshi XuQuan YuanChenchen ZhouPublished in: International journal of oral science (2020)
As a member of the AFF (AF4/FMR2) family, AFF4 is a transcription elongation factor that is a component of the super elongation complex. AFF4 serves as a scaffolding protein that connects transcription factors and promotes gene transcription through elongation and chromatin remodelling. Here, we investigated the effect of AFF4 on human dental follicle cells (DFCs) in osteogenic differentiation. In this study, we found that small interfering RNA-mediated depletion of AFF4 resulted in decreased alkaline phosphatase (ALP) activity and impaired mineralization. In addition, the expression of osteogenic-related genes (DLX5, SP7, RUNX2 and BGLAP) was significantly downregulated. In contrast, lentivirus-mediated overexpression of AFF4 significantly enhanced the osteogenic potential of human DFCs. Mechanistically, we found that both the mRNA and protein levels of ALKBH1, a critical regulator of epigenetics, changed in accordance with AFF4 expression levels. Overexpression of ALKBH1 in AFF4-depleted DFCs partially rescued the impairment of osteogenic differentiation. Our data indicated that AFF4 promoted the osteogenic differentiation of DFCs by upregulating the transcription of ALKBH1.
Keyphrases
- transcription factor
- mesenchymal stem cells
- endothelial cells
- bone marrow
- induced apoptosis
- poor prognosis
- binding protein
- cell proliferation
- cell cycle arrest
- dna binding
- computed tomography
- long non coding rna
- cell death
- mass spectrometry
- climate change
- dna damage
- high resolution
- human health
- oral health
- dna methylation
- oxidative stress
- artificial intelligence
- single molecule
- data analysis