<p>Long Non-Coding RNA H19 Participates in Periodontal Inflammation via Activation of Autophagy</p>

Abstract

Purpose: Periodontitis is the leading cause of tooth loss. The role of long non-coding RNA (lncRNA) in periodontal inflammation remains unclear. The aim of this study was to investigate the role of lncRNA H19 in periodontitis and its possible regulation of autophagy in periodontitis. Material and Methods: Inflammation level was determined by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) in periodontal ligament cells (PDLCs). Western blotting, flow cytometric analysis, and immunofluorescence staining were used to detect the autophagy flux. Overexpression or knockdown of H19 was used to confirm its function. Ligature-induced periodontitis model in mice and periodontitis-affected human gingival tissue were used in vivo. RNA sequencing was performed to determine the differentially expressed genes. Results: Autophagy was significantly increased in PDLCs after inflammatory stimulation as well as in a ligature-induced periodontitis model in mice and periodontitis-affected human gingival tissue. During the inflammatory process, H19 expression was also significantly upregulated. Further, the levels of autophagic markers were significantly upregulated after overexpressing H19 in PDLCs, and the increased autophagic activity induced by inflammatory stimulation was reversed by H19 knockdown. RNA sequencing showed that the expression profiles of mRNAs were significantly altered after H19 overexpression, and the differentially expressed genes were enriched in the PI3K/AKT signaling pathway, which was confirmed by the decreased p-AKT protein expression in the H19 overexpression group. Conclusion: Periodontal inflammation activates autophagy flux, and H19 mediates the activation of autophagy via AKT pathway in periodontitis. This study expands our understanding of molecular regulation in periodontitis.

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

“…lncRNA H19 has been shown to be an important factor in autophagy [76,77] and has attracted attention for its interaction with periodontitis [78,79]. In PDLCs of ligated mice, autophagy was significantly increased and H19 expression was also significantly upregulated during inflammation [80].…”

The Expression and Regulatory Roles of Long Non-Coding RNAs in Periodontal Ligament Cells: A Systematic Review

“…Table 3 presents 18 studies that investigated the role of lncRNAs in regulating cellular processes in PDL cells in the presence or absence of stimuli, including studies that compared H-PDL and P-PDL cells [ 60 , 61 , 62 , 63 , 64 , 65 ]. These studies also explored the role of lncRNAs in lipopolysaccharide (LPS)-induced inflammation [ 66 , 67 , 68 , 69 , 70 , 71 ], tumor necrosis factor-alpha (TNF-α)-induced inflammation [ 72 ], mechanical stress [ 73 , 74 , 75 ], hypoxia [ 76 ], and oxidative stress [ 77 ]. To review the outcomes of lncRNA involvement, cell proliferation, apoptosis, inflammatory responses, autophagy, migration, and root resorption were examined.…”

Identification and integrated analysis of differentially expressed long non‐coding RNAs associated with periodontitis in humans

“…In addition, research suggests that H19 could enhance the osteogenic differentiation of human bone marrow mesenchymal stem cell and bone formation via the miR‐675‐TGF‐β1‐Smad3‐HDAC signalling pathway, whereas knockdown of H19 suppresses these effects. 36 Recently, Guo et al 37 found that H19 participates in periodontal inflammation by activating autophagy. However, the potential role of H19 as a ceRNA in periodontitis has rarely been reported.…”