{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T17:23:47Z","timestamp":1781889827790,"version":"3.54.5"},"reference-count":85,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Periodontal disease is a prevalent inflammatory disorder that can lead to severe oral complications. Recent studies increasingly underline the role of endoplasmic reticulum (ER) stress in its pathogenesis. Experimental models using inflammatory agents such as lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-\u03b1), and ligature-induced periodontitis in rodents, as well as chemical hypoxia, have consistently demonstrated the activation of unfolded protein response (UPR) pathways in periodontal cells. Key ER stress markers, including CHOP, GRP78, PERK, and ATF6, were upregulated in periodontal ligament cells, stem cells, and gingival epithelial cells under these conditions. While ER stress in periodontitis is primarily associated with detrimental outcomes such as apoptosis and inflammation, it may also have a physiological role in bone remodeling via the PERK-eIF2\u03b1-ATF4 axis. Importantly, several ER stress-modulating agents\u2014such as oridonin, melatonin, and exosomes derived from M2 macrophages\u2014have shown therapeutic potential by reducing stress marker expression and limiting periodontal damage. These findings suggest that targeting ER stress may offer a novel therapeutic strategy. Future human studies are essential to determine whether a combined approach targeting inflammation and ER stress could more effectively halt or reverse periodontal tissue destruction, while also assessing the long-term safety of ER stress modulation.<\/jats:p>","DOI":"10.3390\/ijms26199620","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T09:38:08Z","timestamp":1759397888000},"page":"9620","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Role of Endoplasmic Reticulum Stress in the Development of Periodontitis\u2014From Experimental Cell and Animal Models to Humans"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6014-5044","authenticated-orcid":false,"given":"Sebastian","family":"Gawlak-Socka","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical University of Lodz, \u017beligowskiego 7\/9, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Soko\u0142owska","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical University of Lodz, \u017beligowskiego 7\/9, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9277-0875","authenticated-orcid":false,"given":"Gabriela","family":"Henrykowska","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, Medical University of Lodz, \u017beligowskiego 7\/9, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Kowalczyk","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical University of Lodz, \u017beligowskiego 7\/9, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"K\u0142osek","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Medical University of Lodz, Pomorska 251, 92-213 Lodz, Poland"},{"name":"Department of Periodontology and Oral Mucosal Diseases, Medical University of Lodz, Pomorska 251, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3452-5748","authenticated-orcid":false,"given":"Anna","family":"Wiktorowska-Owczarek","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical University of Lodz, \u017beligowskiego 7\/9, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1111\/idj.12630","article-title":"Current Concepts in the Management of Periodontitis","volume":"71","author":"Kwon","year":"2021","journal-title":"Int. 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