Role of histone deacetylase 9 in human periodontal ligament stem cells autophagy in a tumour necrosis factor α-induced inflammatory environment

Abstract

Histone deacetylases (HDACs) play important roles in the post-translational modification of histones, which can affect the biological properties of cells, thereby altering disease progression and outcomes. However, it remains unclear how HDAC9, a class II HDAC, affects the autophagy of human periodontal ligament stem cells (hPDLSCs). We aimed to identify its role in autophagy in hPDLSCs in an inflammatory environment and to explore the potential regulatory mechanisms. A rat periodontitis model was induced by ligating the molars with silk thread. Expression of autophagy-related genes and TNF-α was elevated in this model. TNF-α was used to stimulate hPDLSCs to establish an inflammatory environment. In the TNF-α-stimulated hPDLSCs, the expression of ATG7, ATG12, Beclin-1, LC3 and HDAC9 was upregulated, and that of p62 was downregulated. When HDAC9 expression was inhibited, autophagy-related genes expression was downregulated, and p62 expression was upregulated in TNF-α-treated hPDLSCs, indicating that autophagy was inhibited under these conditions. ERK pathway inhibition significantly reduced HDAC9-mediated autophagy in TNF-α-treated hPDLSCs. These findings reveal that autophagy occurred in our rat periodontitis model and that HDAC9 regulated autophagy via ERK pathways in hPDLSCs in the inflammatory environment. HDAC9 is therefore a potential target for the treatment of periodontitis.