{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:12:33Z","timestamp":1787015553976,"version":"build-2736575974"},"reference-count":15,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515110163"],"award-info":[{"award-number":["2021A1515110163"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Oral Rehabilitation"],"published-print":{"date-parts":[[2024,4]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Blocking Delta\u2010like 4 (DLL4)\/Notch has emerged as a promising therapeutic target for the treatment of tumours by deregulating angiogenesis. However, DLL4\/Notch serves as a negative regulator of angiogenesis in multiple organs while acting as a positive regulator of H\u2010type angiogenesis in postnatal long bones. Therefore, the effect of DLL4\/Notch signalling blockade on mandibular condylar osteogenesis attracted our attention.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To explore the effect of blocking DLL4\/Notch on mandibular advancement (MA)\u2010induced condylar osteogenesis.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Six\u2010week\u2010old young male C57BL\/6J mice (\n n<\/jats:italic>\n \u2009=\u200940) were randomly divided into four groups: control group, MA group, MA\u2009+\u2009Anti\u2010DLL4 group and MA\u2009+\u2009IgG group. Of note, IgG served as the isotype control for the anti\u2010DLL4. The femurs, tibias and mandibular condyles were collected after sacrificing mice on Day 31 for morphology, micro\u2010computed tomography, immunofluorescence, histology and immunohistochemistry evaluation.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n First, DLL4\/Notch blockade shortened femoral length and reduced bone mass by inhibiting H\u2010type angiogenesis. Second, DLL4\/Notch blockade disrupted MA\u2010induced condylar head volume and quality by inhibiting H\u2010type angiogenesis. Mechanistically, blocking DLL4\/Notch reduced the number of runt\u2010related transcription factor 2\n +<\/jats:sup>\n (RUNX2\n +<\/jats:sup>\n ) early osteoprogenitors and the expression of Noggin protein in the condylar subchondral bone by inhibiting H\u2010type angiogenesis. In addition, blockade of DLL4\/Notch also destroyed the condylar cartilage layer.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n DLL4\/Notch blockade results in shortened femurs and osteopenia, as well as impaired MA\u2010induced condylar osteogenic volume and quality in growing mice by inhibiting H\u2010type angiogenesis. Therefore, when blocking DLL4\/Notch is used as a treatment target for diseases, attention should be paid to its impact on the bone mass of mandibular condyle.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/joor.13642","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T13:37:36Z","timestamp":1702647456000},"page":"754-761","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["DLL4<\/scp>\n \/Notch blockade disrupts mandibular advancement\u2010induced condylar osteogenesis by inhibiting H\u2010type angiogenesis"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0501-4009","authenticated-orcid":false,"given":"Yun","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Orthodontics, Stomatological Hospital, School of Stomatology Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2029-4064","authenticated-orcid":false,"given":"Hegang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Stomatological Hospital, School of Stomatology Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407290101"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.11.1313"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05577"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.003244"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05313"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05355"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13146"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13145"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08751"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/joor.13410"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-023-04985-5"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345211002120"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.306926"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05571"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-1604"}],"container-title":["Journal of Oral Rehabilitation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/joor.13642","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:13:00Z","timestamp":1709251980000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/joor.13642"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,15]]},"references-count":15,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1111\/joor.13642"],"URL":"https:\/\/doi.org\/10.1111\/joor.13642","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/JOOR.13642\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JOOR.13642\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JOOR.13642\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JOOR.13642\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JOOR.13642\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JOOR.13642\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JOOR.13642\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0305-182X","1365-2842"],"issn-type":[{"value":"0305-182X","type":"print"},{"value":"1365-2842","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,15]]},"assertion":[{"value":"2023-09-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}