{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T08:57:43Z","timestamp":1788598663227,"version":"build-2803163510"},"reference-count":95,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Interdisciplinary Center of Clinical Research of the Medical Faculty Jena","award":["MSP-08"],"award-info":[{"award-number":["MSP-08"]}]},{"name":"Program for the Support of Third-Party Funding for Young Scientists 2018 Program Line B (Basic) of the Friedrich-Schiller University Jena","award":["DRM\/2018-10"],"award-info":[{"award-number":["DRM\/2018-10"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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 Porphyromonas gingivalis 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 COX2 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.<\/jats:p>","DOI":"10.3390\/cells11060955","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T11:46:47Z","timestamp":1646912807000},"page":"955","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Palmitate-Triggered COX2\/PGE2-Related Hyperinflammation in Dual-Stressed PdL Fibroblasts Is Mediated by Repressive H3K27 Trimethylation"],"prefix":"10.3390","volume":"11","author":[{"given":"Lisa","family":"Schuldt","sequence":"first","affiliation":[{"name":"Orthodontic Research Laboratory, Department of Orthodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Reimann","sequence":"additional","affiliation":[{"name":"Section of Geriodontics, Department of Conservative Dentistry and Periodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"von Brandenstein","sequence":"additional","affiliation":[{"name":"Orthodontic Research Laboratory, Department of Orthodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Steinmetz","sequence":"additional","affiliation":[{"name":"Orthodontic Research Laboratory, Department of Orthodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"D\u00f6ding","sequence":"additional","affiliation":[{"name":"Section of Geriodontics, Department of Conservative Dentistry and Periodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8046-0394","authenticated-orcid":false,"given":"Ulrike","family":"Schulze-Sp\u00e4te","sequence":"additional","affiliation":[{"name":"Section of Geriodontics, Department of Conservative Dentistry and Periodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collin","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Center for Dental, Oral and Maxillofacial Medicine, Department of Orthodontics, University Hospital Jena, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9347-0172","authenticated-orcid":false,"given":"Judit","family":"Symmank","sequence":"additional","affiliation":[{"name":"Orthodontic Research Laboratory, Department of Orthodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1007\/s40496-017-0156-9","article-title":"Current Concepts of Epigenetics and Its Role in Periodontitis","volume":"4","author":"Larsson","year":"2017","journal-title":"Curr. 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