{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:42:51Z","timestamp":1787071371399,"version":"build-2736575974"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"\n AIMS:<\/jats:title>\n \n Endothelin-1 (ET-1) increased bone resorption during orthodontic tooth movement (OTM) in animal models, suggesting potential clinical applications for accelerating OTM. However, the molecular mechanisms by which ET-1 regulates the expression of genes involved in OTM in human periodontal ligament (hPDL) cells remain unexplored. This study investigated the effect of ET-1 on vascular endothelial growth factor (\n VEGF<\/jats:italic>\n ) and cyclooxygenase-2 (\n COX-2<\/jats:italic>\n ) expression and PGE2 production in hPDL cells.\n <\/jats:p>\n <\/jats:sec>\n \n MATERIALS AND METHODS:<\/jats:title>\n \n hPDL cells were treated with 1, 10, and 100 pM ET-1 for 24 h, and cytotoxicity was assessed by MTT assay. The time-course and dose-response effects of ET-1 on\n VEGF<\/jats:italic>\n expression were evaluated. For\n COX-2<\/jats:italic>\n expression, cells were treated with 10 pM ET-1 for 0.5, 1, 2, and 4 h. Quantitative polymerase chain reaction was used to measure\n VEGF<\/jats:italic>\n and\n COX-2<\/jats:italic>\n mRNA levels, and enzyme-linked immunosorbent assay was performed to assess PGE2 production. To explore the role of the extracellular signal-regulated kinase (ERK) pathway, cells were pretreated with PD98059 before ET-1 exposure. Statistical significance was determined by one-way analysis of variance or Kruskal\u2013Wallis test.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:title>\n \n ET-1 at 1\u2013100 pM showed no cytotoxic effects. ET-1 did not significantly affect\n VEGF<\/jats:italic>\n expression at any time point or dose tested. In contrast, ET-1 significantly increased\n COX-2<\/jats:italic>\n expression and PGE2 production at 1 h (\n P<\/jats:italic>\n < 0.05). PD98059 did not inhibit ET-1-induced\n COX-2<\/jats:italic>\n expression, suggesting that ET-1 regulates\n COX-2<\/jats:italic>\n via an ERK-independent mechanism.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSION:<\/jats:title>\n \n ET-1 upregulates\n COX-2<\/jats:italic>\n expression and PGE2 synthesis in hPDL cells through an ERK-independent pathway, while exerting no significant effect on\n VEGF<\/jats:italic>\n expression. Further studies are warranted to assess the therapeutic potential of ET-1 in accelerating OTM.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/jos.jos_146_25","type":"journal-article","created":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T14:00:35Z","timestamp":1771682435000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Endothelin-1 upregulates cyclooxygenase-2 expression and prostaglandin E2 synthesis in human periodontal ligament cells\u2014an in vitro study"],"prefix":"10.4103","volume":"15","author":[{"given":"Supachai","family":"Unmanatakoon","sequence":"first","affiliation":[{"name":"Department of Orthodontics, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand"},{"name":"Division of Dentistry, Phukhiao Chaloem Phra Kiat Hospital, Chaiyaphum, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supaporn","family":"Suttamanatwong","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,2]]},"reference":[{"key":"R1-20260407","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.ajodo.2017.09.016","article-title":"Age-dependent biologic response to orthodontic forces","volume":"153","author":"Alikhani","year":"2018","journal-title":"Am J Orthod Dentofacial Orthop"},{"key":"R2-20260407","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.kjms.2018.01.007","article-title":"Orthodontic tooth movement: The biology and clinical implications","volume":"34","author":"Li","year":"2018","journal-title":"Kaohsiung J Med 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