Palmitate-Triggered COX2/PGE2-Related Hyperinflammation in Dual-Stressed PdL Fibroblasts Is Mediated by Repressive H3K27 Trimethylation
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 b...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-03-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/6/955 |
| _version_ | 1797472379648081920 |
|---|---|
| author | Lisa Schuldt Michael Reimann Katrin von Brandenstein Julia Steinmetz Annika Döding Ulrike Schulze-Späte Collin Jacobs Judit Symmank |
| author_facet | Lisa Schuldt Michael Reimann Katrin von Brandenstein Julia Steinmetz Annika Döding Ulrike Schulze-Späte Collin Jacobs Judit Symmank |
| author_sort | Lisa Schuldt |
| collection | DOAJ |
| description | 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 <i>Porphyromonas gingivalis</i> 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 <i>COX2</i> 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. |
| first_indexed | 2024-03-09T20:01:02Z |
| format | Article |
| id | doaj.art-7ba44ea8de5a4b52bebf0266c0be9a5b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:01:02Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-7ba44ea8de5a4b52bebf0266c0be9a5b2023-11-24T00:43:49ZengMDPI AGCells2073-44092022-03-0111695510.3390/cells11060955Palmitate-Triggered COX2/PGE2-Related Hyperinflammation in Dual-Stressed PdL Fibroblasts Is Mediated by Repressive H3K27 TrimethylationLisa Schuldt0Michael Reimann1Katrin von Brandenstein2Julia Steinmetz3Annika Döding4Ulrike Schulze-Späte5Collin Jacobs6Judit Symmank7Orthodontic Research Laboratory, Department of Orthodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, GermanySection of Geriodontics, Department of Conservative Dentistry and Periodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, GermanyOrthodontic Research Laboratory, Department of Orthodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, GermanyOrthodontic Research Laboratory, Department of Orthodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, GermanySection of Geriodontics, Department of Conservative Dentistry and Periodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, GermanySection of Geriodontics, Department of Conservative Dentistry and Periodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, GermanyCenter for Dental, Oral and Maxillofacial Medicine, Department of Orthodontics, University Hospital Jena, 07743 Jena, GermanyOrthodontic Research Laboratory, Department of Orthodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, GermanyThe 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 <i>Porphyromonas gingivalis</i> 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 <i>COX2</i> 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.https://www.mdpi.com/2073-4409/11/6/955periodontitistooth movementobesitypalmitic acidhistone modificationinflammation |
| spellingShingle | Lisa Schuldt Michael Reimann Katrin von Brandenstein Julia Steinmetz Annika Döding Ulrike Schulze-Späte Collin Jacobs Judit Symmank Palmitate-Triggered COX2/PGE2-Related Hyperinflammation in Dual-Stressed PdL Fibroblasts Is Mediated by Repressive H3K27 Trimethylation Cells periodontitis tooth movement obesity palmitic acid histone modification inflammation |
| title | Palmitate-Triggered COX2/PGE2-Related Hyperinflammation in Dual-Stressed PdL Fibroblasts Is Mediated by Repressive H3K27 Trimethylation |
| title_full | Palmitate-Triggered COX2/PGE2-Related Hyperinflammation in Dual-Stressed PdL Fibroblasts Is Mediated by Repressive H3K27 Trimethylation |
| title_fullStr | Palmitate-Triggered COX2/PGE2-Related Hyperinflammation in Dual-Stressed PdL Fibroblasts Is Mediated by Repressive H3K27 Trimethylation |
| title_full_unstemmed | Palmitate-Triggered COX2/PGE2-Related Hyperinflammation in Dual-Stressed PdL Fibroblasts Is Mediated by Repressive H3K27 Trimethylation |
| title_short | Palmitate-Triggered COX2/PGE2-Related Hyperinflammation in Dual-Stressed PdL Fibroblasts Is Mediated by Repressive H3K27 Trimethylation |
| title_sort | palmitate triggered cox2 pge2 related hyperinflammation in dual stressed pdl fibroblasts is mediated by repressive h3k27 trimethylation |
| topic | periodontitis tooth movement obesity palmitic acid histone modification inflammation |
| url | https://www.mdpi.com/2073-4409/11/6/955 |
| work_keys_str_mv | AT lisaschuldt palmitatetriggeredcox2pge2relatedhyperinflammationindualstressedpdlfibroblastsismediatedbyrepressiveh3k27trimethylation AT michaelreimann palmitatetriggeredcox2pge2relatedhyperinflammationindualstressedpdlfibroblastsismediatedbyrepressiveh3k27trimethylation AT katrinvonbrandenstein palmitatetriggeredcox2pge2relatedhyperinflammationindualstressedpdlfibroblastsismediatedbyrepressiveh3k27trimethylation AT juliasteinmetz palmitatetriggeredcox2pge2relatedhyperinflammationindualstressedpdlfibroblastsismediatedbyrepressiveh3k27trimethylation AT annikadoding palmitatetriggeredcox2pge2relatedhyperinflammationindualstressedpdlfibroblastsismediatedbyrepressiveh3k27trimethylation AT ulrikeschulzespate palmitatetriggeredcox2pge2relatedhyperinflammationindualstressedpdlfibroblastsismediatedbyrepressiveh3k27trimethylation AT collinjacobs palmitatetriggeredcox2pge2relatedhyperinflammationindualstressedpdlfibroblastsismediatedbyrepressiveh3k27trimethylation AT juditsymmank palmitatetriggeredcox2pge2relatedhyperinflammationindualstressedpdlfibroblastsismediatedbyrepressiveh3k27trimethylation |