{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:02:43Z","timestamp":1788825763973,"version":"build-2803163510"},"reference-count":39,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100003785","name":"Guangdong Medical Research Foundation","doi-asserted-by":"publisher","award":["A2022385"],"award-info":[{"award-number":["A2022385"]}],"id":[{"id":"10.13039\/501100003785","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870770"],"award-info":[{"award-number":["81870770"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370958"],"award-info":[{"award-number":["82370958"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82401125"],"award-info":[{"award-number":["82401125"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003456","name":"Guangzhou Municipal Bureau of Agriculture","doi-asserted-by":"publisher","award":["2023A04J2155"],"award-info":[{"award-number":["2023A04J2155"]}],"id":[{"id":"10.13039\/501100003456","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:p>Circadian rhythm disruption is thought to be associated with periodontitis, and molecular clock genes play critical roles in regulating bone homeostasis. However, the specific contribution of molecular clock genes to alveolar bone resorption caused by periodontitis is poorly understood. In this study, we introduced a novel Periodontitis Circadian Rhythm Score (PeriCRS) model that was established through machine learning using periodontal transcriptomic data from periodontitis clinical cohorts in the Gene Expression Omnibus (GEO) database. This approach revealed the potential regulatory role of circadian rhythm disruption in periodontitis and identified key molecular clock genes associated with alveolar bone destruction. Moreover, we established an experimental periodontitis model with circadian rhythm disturbance via periodontal ligation in mice exposed to a 6-h advanced LD12:12 cycle every 2 d. Our bioinformatics analysis revealed that NR1D1, which encodes REV-ERB\u03b1, is a pivotal factor in the impact of circadian rhythm disruption on periodontitis in periodontal tissues. Next, we confirmed the abnormal expression of the molecular clock gene Rev-erb\u03b1 in inflammatory periodontal tissue in mice and confirmed that circadian rhythm disruption altered REV-ERB\u03b1 expression. Furthermore, the activation of REV-ERB\u03b1 with the agonist SR9009 notably decreased RANKL-induced osteoclast differentiation and suppressed the expression of osteoclast-related factors. Subsequent in vivo experiments demonstrated that SR9009 mitigated alveolar bone loss caused by periodontitis. Mechanistically, we found that the IL-22-STAT3 pathway inhibited REV-ERB\u03b1 expression and modulated RANKL-induced osteoclast differentiation in vitro. Our results elucidate the role of REV-ERB\u03b1 in osteoclastogenesis and suggest a potential new therapeutic avenue for addressing alveolar bone resorption associated with periodontitis.<\/jats:p>","DOI":"10.1177\/00220345241290444","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T08:36:52Z","timestamp":1733301412000},"page":"193-203","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["REV-ERB\u03b1 Inhibits Osteoclastogenesis and Protects against Alveolar Bone Loss"],"prefix":"10.1177","volume":"104","author":[{"given":"C.","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Periodontology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China"},{"name":"Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China"},{"name":"Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China"},{"name":"Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China"},{"name":"Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China"},{"name":"Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China"},{"name":"Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China"},{"name":"Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China"},{"name":"Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China"},{"name":"Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1359-0252","authenticated-orcid":false,"given":"C.","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China"},{"name":"Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China"},{"name":"Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,12,4]]},"reference":[{"key":"bibr1-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz4530"},{"key":"bibr2-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.19-0105"},{"key":"bibr3-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2007.03.001"},{"key":"bibr4-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1177\/07487304231179595"},{"key":"bibr5-00220345241290444","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00867"},{"key":"bibr6-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010617-052645"},{"key":"bibr7-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-022-00884-1"},{"key":"bibr8-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1111\/iej.12274"},{"key":"bibr9-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12461"},{"key":"bibr10-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2014.06.011"},{"key":"bibr11-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2015.02.020"},{"key":"bibr12-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1080\/07420528.2024.2305212"},{"issue":"1","key":"bibr13-00220345241290444","first-page":"34","volume":"43","author":"Kim K","year":"2020","journal-title":"Mol Cell"},{"key":"bibr14-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.38"},{"key":"bibr15-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03896-7"},{"key":"bibr16-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40927-1"},{"key":"bibr17-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12682"},{"key":"bibr18-00220345241290444","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010374"},{"key":"bibr19-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04013-w"},{"key":"bibr20-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-021-03068-x"},{"key":"bibr21-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12654"},{"key":"bibr22-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12946"},{"key":"bibr23-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13508"},{"key":"bibr24-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4017"},{"key":"bibr25-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw7365"},{"key":"bibr26-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1038\/nature00965"},{"key":"bibr27-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2014.06.005"},{"key":"bibr28-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2021.06.024"},{"issue":"1","key":"bibr29-00220345241290444","first-page":"100547","volume":"5","author":"Shen Z","year":"2023","journal-title":"Innovation (Camb)"},{"key":"bibr30-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600825RRR"},{"key":"bibr31-00220345241290444","doi-asserted-by":"crossref","unstructured":"Song W, Ye L, Tang Q, Lu X, Huang X, Xie M, Yu S, Yuan Z, Chen L. 2024. REV-ERB\u03b1 attenuates refractory periapical periodontitis via M1 polarization: an in vitro and in vivo study. Int Endod J. 57(4):451\u2013463.","DOI":"10.1111\/iej.14024"},{"key":"bibr32-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1093\/icb\/icac140"},{"key":"bibr33-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.08.012"},{"key":"bibr34-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.106544"},{"key":"bibr35-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan0677"},{"key":"bibr36-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06568-5"},{"key":"bibr37-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.102866"},{"key":"bibr38-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-021-00919-4"},{"key":"bibr39-00220345241290444","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmz078"}],"container-title":["Journal of Dental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00220345241290444","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/00220345241290444","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00220345241290444","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:09:02Z","timestamp":1777496942000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/00220345241290444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,4]]},"references-count":39,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1177\/00220345241290444"],"URL":"https:\/\/doi.org\/10.1177\/00220345241290444","relation":{},"ISSN":["0022-0345","1544-0591"],"issn-type":[{"value":"0022-0345","type":"print"},{"value":"1544-0591","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,4]]}}}