{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:04:05Z","timestamp":1792627445896,"version":"4.5.0"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,6,5]],"date-time":"2021-06-05T00:00:00Z","timestamp":1622851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The immune checkpoint programmed cell death 1 (PD\u20101): PD\u20101 ligand 1 (PD\u2010L1) pathway plays a crucial role in maintaining immune tolerance and preventing tissue damages by excessive immune responses. PD\u2010L1 is physiologically expressed and upregulated in keratinocytes (KCs) in the oral cavity. We here investigated the contribution of PD\u2010L1 that was overexpressed in gingival basal KCs in a ligature\u2010induced periodontitis model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Wild\u2010type (WT) BALB\/c and K14\/PD\u2010L1 transgenic (tg) mice, in which PD\u2010L1 was overexpressed in basal KCs under control of the keratin 14 promoter, were used. To induce periodontitis, a 9\u20100 silk ligature was placed around the upper right second molar, and lipopolysaccharide from <jats:italic>Porphyromonas gingivalis<\/jats:italic> was applied on the suture. Gingival tissues were collected on day 7, after which histological analyses were performed, including by hematoxylin and eosin and tartrate\u2010resistant acid phosphate staining (TRAP) and quantitative PCR for proinflammatory cytokines and bone metabolism\u2010related genes. Alveolar bone loss at 7\u00a0weeks after ligature placement was assessed by micro\u2010computed tomography analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PD\u2010L1 was overexpressed in the basal KCs of all gingival epithelia in K14\/PD\u2010L1tg mice. Early ligature\u2010induced periodontal inflammation, as assessed based on histological changes, elevation of proinflammatory cytokine (IL\u20101\u03b2, IL\u20106, TNF\u2010\u03b1) expression, periodontal ligament degeneration, and osteoclastogenesis as assessed by Rankl and Opg expression and TRAP+ cells, was markedly impaired in K14\/PD\u2010L1tg mice. Alveolar bone resorption at a late time point was also clearly minimized in K14\/PD\u2010L1tg mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Overexpression of PD\u2010L1 in gingival basal keratinocytes in K14\/PD\u2010L1tg mice reduces periodontal inflammation and alveolar bone resorption in a ligature\u2010induced periodontitis model.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jper.21-0017","type":"journal-article","created":{"date-parts":[[2021,5,22]],"date-time":"2021-05-22T08:29:50Z","timestamp":1621672190000},"page":"146-155","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Overexpression of PD\u2010L1 in gingival basal keratinocytes reduces periodontal inflammation in a ligature\u2010induced periodontitis 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