{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:28:49Z","timestamp":1790778529983,"version":"4.1.0"},"reference-count":29,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071146"],"award-info":[{"award-number":["82071146"]}],"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":["82171002"],"award-info":[{"award-number":["82171002"]}],"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":["82171003"],"award-info":[{"award-number":["82171003"]}],"id":[{"id":"10.13039\/501100001809","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":[[2026,8]]},"abstract":"<jats:p>\n                    Osteoarthritis (OA) is the most prevalent degenerative disorder of the temporomandibular joint (TMJ), with aging as a major risk factor. Although circadian clocks are essential for maintaining tissue homeostasis and metabolic balance, the influence of aging on tissue-specific circadian regulation of TMJ homeostasis remains unclear. Here, using aged mice and transgenic mouse models, we demonstrated that the mesenchymal circadian clock is indispensable for preserving TMJ osteochondral integrity during aging. Loss of the core circadian regulator\n                    <jats:italic toggle=\"yes\">Bmal1<\/jats:italic>\n                    in mesenchymal cells leads to progressive osteochondral abnormalities in TMJ condyles, including disrupted cartilage stratification, thinning of the cartilage layer, and abnormal subchondral bone architecture, resembling age-related TMJ degeneration. Mechanistically, BMAL1 directly regulates\n                    <jats:italic toggle=\"yes\">Prg4<\/jats:italic>\n                    transcription, suppresses aberrant transforming growth factor \u03b2 (TGF-\u03b2) signaling to maintain osteochondral homeostasis, and preserves the circadian rhythmicity of lipid metabolism. Notably, circadian-timed intra-articular administration of recombinant PRG4 at night, corresponding to its physiological expression peak, partially restores the cartilage integrity in both\n                    <jats:italic toggle=\"yes\">Bmal1<\/jats:italic>\n                    mutant and aged mice. Collectively, our findings reveal a mesenchymal clock-driven PRG4\u2013TGF-\u03b2 signaling axis that integrates circadian regulation with osteochondral homeostasis while also linking lipid metabolism, establishing chronotherapeutic PRG4 supplementation as a potential strategy to mitigate age-associated TMJ degeneration.\n                  <\/jats:p>","DOI":"10.1177\/00220345251401502","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T04:57:28Z","timestamp":1766033848000},"page":"1186-1194","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Mesenchymal Clock Regulates TMJ Homeostasis and Lipid Metabolic Rhythms with Age"],"prefix":"10.1177","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4126-8620","authenticated-orcid":false,"given":"S.","family":"Cha","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Clinical Research Center for Oral Diseases &amp; Department of Orthodontics, West China School of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Clinical Research Center for Oral Diseases &amp; Department of Orthodontics, West China School of Stomatology, Sichuan University, Chengdu, China"},{"name":"Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Clinical Research Center for Oral Diseases &amp; Department of Orthodontics, West China School of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Clinical Research Center for Oral Diseases &amp; Department of Orthodontics, West China School of Stomatology, Sichuan University, Chengdu, China"},{"name":"Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7153-9001","authenticated-orcid":false,"given":"Q.","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Clinical Research Center for Oral Diseases &amp; Department of Orthodontics, West China School of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Bai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Clinical Research Center for Oral Diseases &amp; Department of Orthodontics, West China School of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910632"},{"key":"e_1_3_2_3_1","doi-asserted-by":"crossref","unstructured":"Cha S et al 2022. Clock-modified mesenchymal stromal cells therapy rescues molecular circadian oscillation and age-related bone loss via miR142-3p\/Bmal1\/YAP signaling axis. Cell Death Discov. 8(1):111. https:\/\/doi.org\/10.1038\/s41420-022-00908-7","DOI":"10.1038\/s41420-022-00908-7"},{"key":"e_1_3_2_4_1","doi-asserted-by":"crossref","unstructured":"Cheng WJ et al 2021. Night shift work and the risk of metabolic syndrome: findings from an 8-year hospital cohort. PLoS One. 16(12):e0261349. https:\/\/doi.org\/10.1371\/journal.pone.0261349","DOI":"10.1371\/journal.pone.0261349"},{"key":"e_1_3_2_5_1","doi-asserted-by":"crossref","unstructured":"Coles JM et al 2010. Loss of cartilage structure stiffness and frictional properties in mice lacking PRG4. Arthritis Rheum. 62(6):1666\u20131674. https:\/\/doi.org\/10.1002\/art.27436","DOI":"10.1002\/art.27436"},{"key":"e_1_3_2_6_1","doi-asserted-by":"crossref","unstructured":"Dudek M et al 2016. The chondrocyte clock gene Bmal1 controls cartilage homeostasis and integrity. J Clin Invest. 126(1):365\u2013376. https:\/\/doi.org\/10.1172\/jci82755","DOI":"10.1172\/JCI82755"},{"key":"e_1_3_2_7_1","doi-asserted-by":"crossref","unstructured":"Fagiani F et al 2022. Molecular regulations of circadian rhythm and implications for physiology and diseases. Signal Transduct Target Ther. 7(1):41. https:\/\/doi.org\/10.1038\/s41392-022-00899-y","DOI":"10.1038\/s41392-022-00899-y"},{"key":"e_1_3_2_8_1","doi-asserted-by":"crossref","unstructured":"Fishbein AB Knutson KL Zee PC. 2021. Circadian disruption and human health. J Clin Invest. 131(19):e148286. https:\/\/doi.org\/10.1172\/jci148286","DOI":"10.1172\/JCI148286"},{"key":"e_1_3_2_9_1","doi-asserted-by":"crossref","unstructured":"Frazier K et al 2023. Gut microbes and the liver circadian clock partition glucose and lipid metabolism. 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