Histone demethylase KDM5A regulates the functions of human periodontal ligament stem cells during periodontitis via the miR-495-3p/HOXC8 axis

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Introduction Periodontitis is the sixth most common human disease and epigenetic regulation is identified to affect the functions of stem cells. This research aims to analyze the role of histone demethylase Lysine-specific demethylase 5A (KDM5A) in human periodontal ligament stem cells (hPDLSCs) with periodontitis. Methods hPDLSCs were treated with porphyromonas gingivalis-lipopolysaccharide (Pg-LPS) and subjected to osteogenic induction. The expression of KDM5A was detected by RT-qPCR and Western blot. Then, KDM5A expression patterns in hPDLSCs were measured and then silenced using shRNA to explore its role in osteogenic differentiation (OD), proliferation, and migration of hPDLSCs. ChIP assay was used to analyze the relationship between KDM5A and miR-495-3p, Western blot was used to detect H3K4me3 and RT-qPCR was used to detect miR-495-3p expression. CPI-455 (specific KDM5 inhibitor) was adopted to confirm the role of H3K4me3, and dual-Luciferase assay indicted the relationship between miR-495-3p and homeobox C8 (HOXC8). A functional rescue experiment was designed to analyze the role of miR-495-3p in hPDLSCs with periodontitis. Results KDM5A was highly expressed in LPS-treated hPDLSCs. Downregulation of KDM5A promoted OD, proliferation, and migration of hPDLSCs. Mechanically, KDM5A inhibited miR-495-3p expression by demethylation of H3K4me3 to enhance HOXC8 transcription. Dow

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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