State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China.
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Cariology and Endodontology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Int J Oral Sci. 2020 Jun 30;12(1):20. doi: 10.1038/s41368-020-0083-9.
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.
作为 AFF（AF4/FMR2）家族的一员，AFF4 是一种转录延伸因子，是超级延伸复合物的组成部分。AFF4 作为一种支架蛋白，连接转录因子并通过延伸和染色质重塑促进基因转录。在这里，我们研究了 AFF4 对人牙囊细胞（DFCs）成骨分化的影响。在这项研究中，我们发现，小干扰 RNA 介导的 AFF4 耗竭导致碱性磷酸酶（ALP）活性降低和矿化受损。此外，成骨相关基因（DLX5、SP7、RUNX2 和 BGLAP）的表达明显下调。相反，慢病毒介导的 AFF4 过表达显著增强了人 DFCs 的成骨潜能。在机制上，我们发现，ALKBH1 的 mRNA 和蛋白水平，一种关键的表观遗传调节剂，与 AFF4 的表达水平一致地发生变化。在 AFF4 耗竭的 DFCs 中转染 ALKBH1 可部分挽救成骨分化受损。我们的数据表明，AFF4 通过上调 ALKBH1 的转录促进 DFCs 的成骨分化。
