{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:05:00Z","timestamp":1789416300092,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30AI27667"],"award-info":[{"award-number":["P30AI27667"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30AR048311"],"award-info":[{"award-number":["P30AR048311"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oral Microbiology"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Liver\u2010X receptors (LXRs) are essential nuclear hormone receptors involved in cholesterol and lipid metabolism. They are also believed to regulate inflammation and physiological and pathological bone turnover. We have previously shown that infection with the periodontal pathogen <jats:italic>Porphyromonas gingivalis<\/jats:italic> (Pg) in mice increases the abundance of CD11b<jats:sup>+<\/jats:sup>c\u2010fms<jats:sup>+<\/jats:sup>Ly6C<jats:sup>hi<\/jats:sup> cells in bone marrow (BM), spleen (SPL), and peripheral blood. These cells also demonstrated enhanced osteoclastogenic activity and a distinctive gene profile following Pg infection. Here, we investigated the role of LXRs in regulating these osteoclast precursors (OCPs) and periodontal bone loss. We found that Pg infection downregulates the gene expression of LXRs, as well as ApoE, a transcription target of LXRs, in CD11b<jats:sup>+<\/jats:sup>c\u2010fms<jats:sup>+<\/jats:sup>Ly6C<jats:sup>hi<\/jats:sup> OCPs. Activation of LXRs by treatment with GW3965, a selective LXR agonist, significantly decreased Pg\u2010induced accumulation of CD11b<jats:sup>+<\/jats:sup>c\u2010fms<jats:sup>+<\/jats:sup>Ly6C<jats:sup>hi<\/jats:sup> population in BM and SPL. GW3965 treatment also significantly suppressed the osteoclastogenic potential of these OCPs induced by Pg infection. Furthermore, the activation of LXRs reduces the abundance of OCPs systemically in BM and locally in the periodontium, as well as mitigates gingival c\u2010fms expression and periodontal bone loss in a ligature\u2010induced periodontitis model. These data implicate a novel role of LXRs in regulating OCP abundance and osteoclastogenic potential in inflammatory bone loss.<\/jats:p>","DOI":"10.1111\/omi.12447","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T14:57:12Z","timestamp":1702911432000},"page":"125-135","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Activation of liver X receptors suppresses the abundance and osteoclastogenic potential of osteoclast precursors and periodontal bone loss"],"prefix":"10.1111","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4126-1955","authenticated-orcid":false,"given":"Yanfang","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pediatric Dentistry School of Dentistry University of Alabama at Birmingham  Birmingham Alabama 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Heersink School of Medicine University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jannet","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry School of Dentistry University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne M","family":"Michalek","sequence":"additional","affiliation":[{"name":"Department of Microbiology Heersink School of Medicine University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry School of Dentistry University of Alabama at Birmingham  Birmingham Alabama 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