{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:02:41Z","timestamp":1788825761862,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T00:00:00Z","timestamp":1706313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["82030070"],"award-info":[{"award-number":["82030070"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014717","name":"National Outstanding Youth Science Fund Project of National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31725011"],"award-info":[{"award-number":["31725011"]}],"id":[{"id":"10.13039\/100014717","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Rev\u2010erb\u03b1 has been reported to regulate the healing of inflammatory lesions through its effect on the immune system in a variety of inflammatory disease. Moreover, the balance of macrophages polarization plays a crucial role in immune response and inflammatory progression. However, in refractory periapical periodontitis (RAP), the role of Rev\u2010erb\u03b1 in inflammatory response and bone resorption by regulating macrophage polarization remains unclarified. The aims of the present study were to investigate the expression of Rev\u2010erb\u03b1 in experimental RAP and to explore the relationship between Rev\u2010erb\u03b1 and macrophage polarization through the application of its pharmacological agonist SR9009 into the <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p><jats:italic>Enterococcus faecalis<\/jats:italic>\u2010induced RAP models were established in SD rats. Histological staining and micro\u2010computed tomography scanning were used to evaluate osteoclastogenesis and alveolar bone resorption. The expression of Rev\u2010erb\u03b1 and macrophage polarization were detected in the periapical tissues from rats by immunofluorescence, flow cytometry, and western blots. Furthermore, immunohistochemical staining and enzyme\u2010linked immunosorbent assay were performed to explore the relationship between Rev\u2010erb\u03b1 and inflammatory cytokines related to macrophage polarization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>Compared to healthy periapical tissue, the expression of Rev\u2010erb\u03b1 was significantly down\u2010regulated in macrophages from inflammatory periapical area, especially in <jats:italic>Enterococcus faecalis<\/jats:italic>\u2010induced periapical lesions, with obvious type\u20101 macrophage (M1)\u2010like dominance and the production of pro\u2010inflammatory cytokines. In addition, Rev\u2010erb\u03b1 activation by SR9009 could induce type\u20102 macrophage (M2)\u2010like polarization in periapical tissue and THP1 cell line, followed by increased secretion of anti\u2010inflammatory cytokines IL\u201010 and TGF\u2010\u03b2. Furthermore, intracanal application of SR9009 reduced the lesion size and promoted the repair of RAP by decreasing the number of osteoclasts and enhancing the formation of mineralized tissue in periapical inflammatory lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Rev\u2010erb\u03b1 played an essential role in the pathogenesis of RAP through its effect on macrophage polarization. Targeting Rev\u2010erb\u03b1 might be a promising and prospective therapy method for the prevention and management of RAP.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iej.14024","type":"journal-article","created":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T09:48:55Z","timestamp":1706348935000},"page":"451-463","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Rev\u2010erb\u03b1 attenuates refractory periapical periodontitis via <scp>M1<\/scp> polarization: An <i>in vitro<\/i> and <i>in vivo<\/i> study"],"prefix":"10.1111","volume":"57","author":[{"given":"W.","family":"Song","sequence":"first","affiliation":[{"name":"Department of Stomatology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"School of Stomatology, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Province Key Laboratory of Oral and 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