Palmitate-Triggered COX2/PGE2-Related Hyperinflammation in Dual-Stressed PdL Fibroblasts Is Mediated by Repressive H3K27 Trimethylation

• Published in: Cells (Basel, Switzerland) Switzerland), 2022-03, Vol.11 (6), p.955
• Main Authors: Schuldt, Lisa, Reimann, Michael, von Brandenstein, Katrin, Steinmetz, Julia, Döding, Annika, Schulze-Späte, Ulrike, Jacobs, Collin, Symmank, Judit
• Format: Article
• Language: English
• Subjects: Alveolar bone; Amino acids; Cells, Cultured; Connective tissues; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Dinoprostone - metabolism; Disease; Epigenetics; Fatty acids; Fibroblasts; Fibroblasts - metabolism; Gene expression; histone modification; Histones; Histones - metabolism; Humans; Humidity; Hyperlipidemia; Inflammation; Interleukin 10; Lipopolysaccharides; Mechanical stimuli; Methylation; Obesity; Orthodontics; Palmitates - metabolism; Palmitic acid; Periodontal diseases; Periodontal Ligament; periodontitis; Prostaglandin E2; tooth movement
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11060955

The interrelationships between periodontal disease, obesity-related hyperlipidemia and mechanical forces and their modulating effects on the epigenetic profile of periodontal ligament (PdL) cells are assumed to be remarkably complex. The PdL serves as a connective tissue between teeth and alveolar bone and is involved in pathogen defense and the inflammatory responses to mechanical stimuli occurring during tooth movement. Altered inflammatory signaling could promote root resorption and tooth loss. Hyperinflammatory COX2/PGE2 signaling was reported for human PdL fibroblasts (HPdLFs) concomitantly stressed with lipopolysaccharides and compressive force after exposure to palmitic acid (PA). The aim of this study was to investigate the extent to which this was modulated by global and gene-specific changes in histone modifications. The expression of key epigenetic players and global H3Kac and H3K27me3 levels were quantitatively evaluated in dual-stressed HPdLFs exposed to PA, revealing a minor force-related reduction in repressive H3K27me3. UNC1999-induced H3K27me3 inhibition reversed the hyperinflammatory responses of dual-stressed PA cultures characterized by increased expression, PGE2 secretion and THP1 adhesion. The reduced expression of the gene encoding the anti-inflammatory cytokine IL-10 and the increased presence of H3K27me3 at its promoter-associated sites were reversed by inhibitor treatment. Thus, the data highlight an important epigenetic interplay between the different stimuli to which the PdL is exposed.